112 results on '"Slomovitz BM"'
Search Results
2. HPV vaccine: breaking down the barriers.
- Author
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Slomovitz BM and Bodurka DC
- Abstract
Although this preventive measure can save lives, ensuring widespread usage presents a unique challenge for practitioners. [ABSTRACT FROM AUTHOR]
- Published
- 2007
3. Comparison of total laparoscopic and abdominal radical hysterectomy for patients with early-stage cervical cancer.
- Author
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Frumovitz M, dos Reis R, Sun CC, Milam MR, Bevers MW, Brown J, Slomovitz BM, and Ramirez PT
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- 2007
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4. Supracervical hysterectomy in patients with advanced epithelial ovarian cancer.
- Author
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Milam MR, Sood AK, King S, Bassett RL Jr., Lu KH, Slomovitz BM, Coleman RL, and Ramirez PT
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- 2007
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5. What you need to know about laparoscopic surgery for endometrial cancer.
- Author
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Ramirez PT and Slomovitz BM
- Abstract
A laparoscopic procedure is an option for many women with endometrial cancer. Here, two expert gynecologic oncologists tell you what the surgery involves and how to select patients for referral. [ABSTRACT FROM AUTHOR]
- Published
- 2007
6. Prophylactic bilateral salpingo-oophorectomy compared with surveillance in women with BRCA mutations.
- Author
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Schmeler KM, Sun CC, Bodurka DC, White KG, Soliman PT, Uyei AR, Erlichman JL, Arun BK, Daniels MS, Rimes SA, Peterson SK, Slomovitz BM, Milam MR, Gershenson DM, and Lu KH
- Published
- 2006
- Full Text
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7. Risk factors for young premenopausal women with endometrial cancer.
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Soliman PT, Oh JC, Schmeler KM, Sun CC, Slomovitz BM, Gershenson DM, Burke TW, and Lu KH
- Published
- 2005
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8. Does tamoxifen use affect prognosis in breast cancer patients who develop endometrial cancer?
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Slomovitz BM, Sun CC, Ramirez PT, Bodurka DC, Diaz P, and Lu KH
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- 2004
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9. Novel biologic therapies for the treatment of endometrial cancer.
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Slomovitz BM and Webb N
- Published
- 2006
10. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome.
- Author
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Schmeler KM, Lynch HT, Chen L, Munsell MF, Soliman PT, Clark MB, Daniels MS, White KG, Boyd-Rogers SG, Conrad PG, Yang KY, Rubin MM, Sun CC, Slomovitz BM, Gershenson DM, and Lu KH
- Published
- 2006
11. Response to Alexandre Andre B A da Costa et al.
- Author
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Monk BJ, Coleman RL, Tewari KS, Randall LM, Pothuri B, Slomovitz BM, and Herzog TJ
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- 2024
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12. Immunotherapy in locally advanced cervix cancer: A critical appraisal of the FDA indication based on ENGOT-CX11/GOG-3047/KEYNOTE-A18.
- Author
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Monk BJ, Tewari KS, Randall LM, Pothuri B, Slomovitz BM, Coleman RL, and Herzog TJ
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- Humans, Female, United States, Immunotherapy methods, Immune Checkpoint Inhibitors therapeutic use, Drug Approval, Uterine Cervical Neoplasms therapy, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms immunology, United States Food and Drug Administration
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- 2024
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13. Approach to radical hysterectomy for cervical cancer after the Laparoscopic Approach to Cervical Cancer trial and associated complications: a National Surgical Quality Improvement Program study.
- Author
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Levin G, Ramirez PT, Wright JD, Slomovitz BM, Hamilton KM, Schneyer RJ, Barnajian M, Nasseri Y, Siedhoff MT, Wright KN, and Meyer R
- Abstract
Background: The Laparoscopic Approach to Cervical Cancer study results revolutionized our understanding of the best surgical management for this disease. After its publication, the guidelines state that the standard and recommended approach for radical hysterectomy is an open abdominal approach. Nevertheless, the effect of the Laparoscopic Approach to Cervical Cancer trial on real-world changes in the surgical approach to radical hysterectomy remains elusive., Objective: This study aimed to investigate the trends and routes of radical hysterectomy and to evaluate postoperative complication rates before and after the Laparoscopic Approach to Cervical Cancer trial (2018)., Study Design: The National Surgical Quality Improvement Program registry was used to examine radical hysterectomy for cervical cancer performed between 2012 and 2022. This study excluded vaginal radical hysterectomies and simple hysterectomies. The primary outcome measures were the trends in the route of surgery (minimally invasive surgery vs laparotomy) and surgical complication rates, stratified by periods before and after the publication of the Laparoscopic Approach to Cervical Cancer trial in 2018 (2012-2017 vs 2019-2022). The secondary outcome measure was major complications associated specifically with the different routes of surgery., Results: Of the 3611 patients included, 2080 (57.6%) underwent laparotomy, and 1531 (42.4%) underwent minimally invasive radical hysterectomy. There was a significant increase in the minimally invasive surgery approach from 2012 to 2017 (45.6% in minimally invasive surgery in 2012 to 75.3% in minimally invasive surgery in 2017; P<.01) and a significant decrease in minimally invasive surgery from 2018 to 2022 (50.4% in minimally invasive surgery in 2018 to 11.4% in minimally invasive surgery in 2022; P<.001). The rate of minor complications was lower in the period before the Laparoscopic Approach to Cervical Cancer trial than after the trial (317 [16.9%] vs 288 [21.3%], respectively; P=.002). The major complication rates were similar before and after the Laparoscopic Approach to Cervical Cancer trial (139 [7.4%] vs 78 [5.8%], respectively; P=.26). The rates of blood transfusions and superficial surgical site infections were lower in the period before the Laparoscopic Approach to Cervical Cancer trial than in the period after the trial (137 [7.3%] vs 133 [9.8%] [P=.012] and 20 [1.1%] vs 53 [3.9%] [P<.001], respectively). In a comparison of minimally invasive surgery vs laparotomy radical hysterectomy during the entire study period, patients in the minimally invasive surgery group had lower rates of minor complications than in those in the laparotomy group (190 [12.4%] vs 472 [22.7%], respectively; P<.001), and the rates of major complications were similar in both groups (100 [6.5%] in the minimally invasive surgery group vs 139 [6.7%] in the laparotomy group; P=.89). In a specific complications analysis, the rates of blood transfusion and superficial surgical site infections were lower in the minimally invasive surgery group than in the laparotomy group (2.4% vs 12.7% and 0.6% vs 3.4%, respectively; P<.001; for both comparisons), and the rate of deep incisional surgical site infections was lower in the minimally invasive surgery group than in the laparotomy group (0.2% vs 0.7%, respectively; P=.048). In the multiple logistic regression analysis, the route of radical hysterectomy was not independently associated with the occurrence of major complications (adjusted odds ratio, 1.02; 95% confidence interval, 0.63-1.65)., Conclusion: Although the proportion of minimally invasive radical hysterectomies decreased abruptly after the Laparoscopic Approach to Cervical Cancer trial, there was no change in the rate of major postoperative complications. In addition, the hysterectomy route was not associated with major postoperative complications., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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14. Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial.
- Author
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Powell MA, Bjørge L, Willmott L, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Gropp-Meier M, Stuckey A, Boere I, Gold MA, Segev Y, Gill SE, Gennigens C, Sebastianelli A, Shahin MS, Pothuri B, Monk BJ, Buscema J, Coleman RL, Slomovitz BM, Ring KL, Herzog TJ, Balas MM, Grimshaw M, Stevens S, Lai DW, McCourt C, and Mirza MR
- Subjects
- Humans, Female, Double-Blind Method, Middle Aged, Aged, Adult, Aged, 80 and over, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local mortality, Progression-Free Survival, Antibodies, Monoclonal, Humanized, Carboplatin administration & dosage, Endometrial Neoplasms drug therapy, Endometrial Neoplasms mortality, Endometrial Neoplasms pathology, Paclitaxel administration & dosage, Paclitaxel adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
Background: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis., Patients and Methods: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint., Results: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis., Conclusions: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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15. A Plain Language Summary of "Dostarlimab for primary advanced or recurrent endometrial cancer".
- Author
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Mirza MR, Chase DM, Slomovitz BM, Christensen RD, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, and Powell MA
- Published
- 2024
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16. Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer.
- Author
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Vergote I, González-Martín A, Fujiwara K, Kalbacher E, Bagaméri A, Ghamande S, Lee JY, Banerjee S, Maluf FC, Lorusso D, Yonemori K, Van Nieuwenhuysen E, Manso L, Woelber L, Westermann A, Covens A, Hasegawa K, Kim BG, Raimondo M, Bjurberg M, Cruz FM, Angelergues A, Cibula D, Barraclough L, Oaknin A, Gennigens C, Nicacio L, Teng MSL, Whalley E, Soumaoro I, and Slomovitz BM
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Middle Aged, Kaplan-Meier Estimate, Progression-Free Survival, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Neoplasm Recurrence, Local drug therapy, Uterine Cervical Neoplasms drug therapy, Uterine Cervical Neoplasms mortality, Uterine Cervical Neoplasms pathology, Antibodies, Monoclonal, Humanized therapeutic use, Oligopeptides therapeutic use
- Abstract
Background: Recurrent cervical cancer is a life-threatening disease, with limited treatment options available when disease progression occurs after first-line combination therapy., Methods: We conducted a phase 3, multinational, open-label trial of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer. Patients were randomly assigned, in a 1:1 ratio, to receive tisotumab vedotin monotherapy (2.0 mg per kilogram of body weight every 3 weeks) or the investigator's choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival., Results: A total of 502 patients underwent randomization (253 were assigned to the tisotumab vedotin group and 249 to the chemotherapy group); the groups were similar with respect to demographic and disease characteristics. The median overall survival was significantly longer in the tisotumab vedotin group than in the chemotherapy group (11.5 months [95% confidence interval {CI}, 9.8 to 14.9] vs. 9.5 months [95% CI, 7.9 to 10.7]), results that represented a 30% lower risk of death with tisotumab vedotin than with chemotherapy (hazard ratio, 0.70; 95% CI, 0.54 to 0.89; two-sided P = 0.004). The median progression-free survival was 4.2 months (95% CI, 4.0 to 4.4) with tisotumab vedotin and 2.9 months (95% CI, 2.6 to 3.1) with chemotherapy (hazard ratio, 0.67; 95% CI, 0.54 to 0.82; two-sided P<0.001). The confirmed objective response rate was 17.8% in the tisotumab vedotin group and 5.2% in the chemotherapy group (odds ratio, 4.0; 95% CI, 2.1 to 7.6; two-sided P<0.001). A total of 98.4% of patients in the tisotumab vedotin group and 99.2% in the chemotherapy group had at least one adverse event that occurred during the treatment period (defined as the period from day 1 of dose 1 until 30 days after the last dose); grade 3 or greater events occurred in 52.0% and 62.3%, respectively. A total of 14.8% of patients stopped tisotumab vedotin treatment because of toxic effects., Conclusions: In patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy. (Funded by Genmab and Seagen [acquired by Pfizer]; innovaTV 301 ClinicalTrials.gov number, NCT04697628.)., (Copyright © 2024 Massachusetts Medical Society.)
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- 2024
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17. Updates in the Use of Targeted Therapies for Gynecologic Cancers.
- Author
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Cantillo E, Blanc-Durand F, Leary A, Slomovitz BM, Fuh K, and Washington C
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- Humans, Female, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Immunotherapy methods, Immunoconjugates therapeutic use, Antineoplastic Agents therapeutic use, Genital Neoplasms, Female drug therapy, Molecular Targeted Therapy
- Abstract
Targeted therapies have changed the treatment landscape in gynecologic cancer. Studies released over the past year have led to the incorporation of immunotherapy (IO) into the treatment for all patients with endometrial and cervical cancers at some point during their disease course. Poly(ADP-ribose) polymerase (PARP) inhibitors continue to play a role in women with ovarian carcinoma, particularly in homologous repair deficient tumors. Furthermore, the benefit of PARP inhibitors in challenging subgroups continues to be elucidated. Biomarker identification has led to the approval or compendium listing of several antibody-drug conjugates (ADCs). This review will update on IO, ADCs, and PARP inhibition for the treatment of gynecologic cancers.
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- 2024
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18. Vulvar cancer management and wrangling recurrent disease: A report from the society of gynecologic oncology journal club.
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Parker JE, Yoshida EJ, Gien LT, Slomovitz BM, and Nagel C
- Abstract
The Society of Gynecologic Oncology (SGO) Journal Club webinar series is an open forum that invites national experts to discuss the literature pertaining to important topics in the management of gynecologic cancers. On August 14th, 2023, SGO hosted a journal club focused on the management of upfront and recurrent vulvar cancer. Our discussants included Dr. Brian M Slomovitz from Mount Sinai Medical Center in Miami Beach, Dr. Emi Yoshida from the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, and Dr. Lilian Gien from the University of Toronto Sunnybrook Odette Cancer Center. During the discussion,we reviewed the progression of vulvar cancer surgery from en bloc resection of the vulva and groins, to partial radical vulvectomy and sentinel lymph nodes. We also reviewed the management of node positive vulvar cancer including published and accruing Groningen International Study on Sentinel Nodes in Vulvar Cancer (GROINSS) trials and other sentinel trials from the Gynecologic Oncology Group (GOG). Here we will also review the literature on the management of recurrent vulvar cancer, highlighting current treatment options and ongoing clinical trials. The following is a report of the journal club presentation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
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- 2023
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19. Low-grade serous ovarian cancer: expert consensus report on the state of the science.
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Grisham RN, Slomovitz BM, Andrews N, Banerjee S, Brown J, Carey MS, Chui H, Coleman RL, Fader AN, Gaillard S, Gourley C, Sood AK, Monk BJ, Moore KN, Ray-Coquard I, Shih IM, Westin SN, Wong KK, and Gershenson DM
- Subjects
- Humans, Female, Consensus, Quality of Life, Carcinoma, Ovarian Epithelial therapy, Peritoneal Neoplasms, Cystadenocarcinoma, Papillary, Cystadenocarcinoma, Serous diagnosis, Cystadenocarcinoma, Serous therapy, Ovarian Neoplasms diagnosis, Ovarian Neoplasms therapy
- Abstract
Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care., Competing Interests: Competing interests: RG reports fees for grants/contracts from Context Therapeutics, Versatem, SpringWorks, Bayer, Novartis; fees for consulting for GSK, AstraZeneca, Natera, Corcept, Intellisphere, SpringWorks, Verastem, Myriad; fees for payment/honoraria from Prime Oncology, MCM Education, OncLive, Aptitude Health, Cardinal Health; fees for leadership/ fiduciary role with NCCN Ovarian Cancer Guidelines Committee Member, and ICLC Precision Therapeutics. BS reports consulting fees for AstraZeneca, Clovis, GSK, Genentech, Onconova, Nuvation, Lilly, EQRx, Myriad, Immunogen, Novocure, and Merck. NA has no conflicts to disclose. SB reports fees for grants/contracts from AstraZeneca, GSK; fees for consulting for AstraZeneca, GSK, Immunogen, Merck Sharpe Dohme, EMD/Merck Serono, Mersana, Novartis, Oncxerna, Seagen, Shattuck Labs, Regeneron, Epsilogen; fees for payment/honoraria from Amgen, AstraZeneca, Clovis, GSK, Immunogen, Merck Sharpe Dohme, Mersana, Pfizer, Roche, Takeda, Novacure; fees for support for attending meetings/travel from AstraZeneca, GSK, Verastem; fees for leadership/fiduciary role from ESMO Director of Membership (2020-2022); and fees for other financial or non-financial interests from Global PI ENGOTov60/GOG3052/RAMP201. JB reports fees for consulting for Caris Life Sciences, AstraZeneca, Verastem, Genentech, GSK Tesaro; fees for participation on a Data Safety Monitoring Board/Advisory Board from Caris, AstraZeneca, GSK Tesaro, Verastem; fees for a leadership/fiduciary role from American Association of Gynecologic Laparoscopy, and Society of Gynecologic Oncology. MSC reports fees for grants/contracts from Canada Research Society, Canadian Institute for Health Research, Ovarian Cancer Canada, BC Cancer Foundation, Department of Defense US Army, Australian Medical Research Fund; fees for payment/honoraria from Verastem; fees for leadership/fiduciary role from Canadian Cancer Trials Group; and fees for stock or stock option from Bausch Health Companies, Illumina, aiGENE, DentalToday, Hexamer Therapeutics. HC reports fees for payment/honoraria from Verastem Oncology. RLC reports fees for grants/contracts from AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, Roche/Genentech; consulting fees from Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, OncoQuest, Onxerna, Regeneron, Roche/Genentech, Novocure, Merck, Abbvie; fees for payment/honoraria from AstraZeneca, Clovis, Roche/Genentech, Merck; fees for participation on a Data Safety Monitoring Board/Advisory Board from VBL Therapeutics, and Eisai/BMS. ANF reports fees for advisory board support from Versatem and PI of the NCI NRG GY019. SG reports fees for patents for United States Patent Nos 10,258,604 & 10,905,659; and fees for participation on a Data Safety Monitoring Board/Advisory Board from Verastem. CG reports fees for grants from AstraZeneca, GSK, Tesaro, Clovis, MSD, BergenBio, Novartis, Aprea, Nucana, Versatem, Roche, Medannexin; fees for consulting from AstraZeneca, MSD, GSK, Tesaro; fees for payment/honoraria from AstraZeneca, MSD, GSK, Tesaro, Clovis, Roche, Nucana, Chugai, Takeda, Cor2Ed, Peervoice; fees for participation on a Data Safety Monitoring Board/Advisory Board from AstraZeneca, MSD, GSK, Tesaro, Roche, Nucana, Chugai; and fees for a leadership/fiduciary role from Scottish Medicines Consortium. AKS reports fees for grants from American Cancer Society Research Professor Award; fees for royalties from EGFL6 antibody; fees for consulting for Merck, GSK, Iylon, ImmunoGen, Onxeo, Kiyatec; fees for leadership/fiduciary role from SGO Board of Directors; and fees from stock/stock options for BioPath. BJM reports fees for consulting for Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Eisai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, Tesaro/GSK, US Oncology Research, VBL, Verastem, Zentalis; fees for payment/honoraria from AstraZeneca, Clovis, Easai, Merck, Myriad, Roche/Genentech, and Tesaro/GSK. KNM reports fees for grants/contracts and participation on a data safety monitoring board from PTC Therapeutics, Lilly, Clovis, Genentech, GSK, Verastem; fees for consulting for AstraZeneca, Aravive, Alkemeres, Addi, Blueprint pharma, Clovis, Eisai, GSK, Genentech/Roche, Hengrui, Immunogen, Inxmed, IMab, Iovance, Lilly, Mereo, Mersana, Merck, Myriad, Norvartis, Novocur, OncXerna, Onconova, Tarveda, VBL Therapeutics, Verastem; fees for payment/honoraria from AstraZeneca, GSK, Immunogen, PRIME, RTP, Medscape, Great Debates and Updates; fees for support for attending meetings/travel from AstraZeneca; and a leadership/fiduciary role with GOG P Associate Director. IRC reports fees for grants/contracts from MSH, Roche, BMS, Novartis, AstraZeneca, Merck, Sereno; fees for consulting for Agenus, Amgen, BMS, AstraZeneca, Roche, GSK, Deciphera, Mersena, Novartis, Clovis, Adaptimmun, DAICHI Sankyo, Immunogen, Blueprint; fees for support for attending meetings/travel from OSE Company (ASCO 2022); fees for participation on a Data Safety Monitoring Board or Advisory Board from Athena trial, Attend trial and AGO-OVAR57 trial. IMS has no conflicts of interest. SNW reports fees for grants/contracts from AstraZeneca, Bayer, Clovis Oncology, AvengeBio, GSK, Mereo, Novartis, Bio-Path, Roche/Genentech, Zentalis; fees for consulting for ZielBio, AstraZeneca, Clovis Oncology, Eisai, Merck, Mereo, Mersana, Seagen, Nuvectis, Verastem, EQRx, GSK, Immunogen, Lilly, Zentalis, Roche/Genentech, Caris, Vincerx, and NGM Bio. KKW reports fees for support for the present manuscript from MD Anderson Ovarian Cancer Moon Shot Program, STAAR Ovarian Cancer Foundation, The Ludemann Family, and Department of Defense Grant (W81XWH-19-1-0169). DG reports fees for support for the present manuscript from Verastem; fees for grants/contracts from National Cancer Institute, Novartis; fees for royalties/licenses from Elsevier, UpToDate; fees for consulting for Genentech, Verastem; fees for payment/honoraria from University of Washington Grand Rounds, Yale University School of Medicine Grand Rounds; fees for support for attending meetings/travel from Society of Gynecologic Oncology Bridges Program, Verastem; fees for participation on a Data Safety Monitoring Board or Advisory Board from Verastem, Aadi, Onconova; fees for leadership/fiduciary role from Chair, International Consortium of Low-Grade Serious Ovarian Cancer; and fees for stock/stock options from J&J, BMS, and Procter and Gamble., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)
- Published
- 2023
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20. Inclusion, diversity, equity, and access (IDEA) in gynecologic cancer clinical trials: A joint statement from GOG foundation and Society of Gynecologic Oncology (SGO).
- Author
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Pothuri B, Blank SV, Myers TK, Hines JF, Randall LM, O'Cearbhaill RE, Slomovitz BM, Eskander RN, Alvarez Secord A, Coleman RL, Walker JL, Monk BJ, Moore KN, O'Malley DM, Copeland LJ, and Herzog TJ
- Subjects
- Female, Humans, Clinical Trials as Topic, Diversity, Equity, Inclusion, Genital Neoplasms, Female therapy, Ovarian Neoplasms
- Published
- 2023
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21. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer.
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Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, and Powell MA
- Subjects
- Female, Humans, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Carboplatin administration & dosage, Carboplatin adverse effects, DNA Mismatch Repair, Double-Blind Method, Immune Checkpoint Inhibitors administration & dosage, Immune Checkpoint Inhibitors adverse effects, Microsatellite Instability, Paclitaxel administration & dosage, Paclitaxel adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Endometrial Neoplasms drug therapy, Endometrial Neoplasms genetics, Endometrial Neoplasms mortality, Endometrial Neoplasms pathology, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local etiology
- Abstract
Background: Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer., Methods: We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. The primary end points were progression-free survival as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and overall survival. Safety was also assessed., Results: Of the 494 patients who underwent randomization, 118 (23.9%) had mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors. In the dMMR-MSI-H population, estimated progression-free survival at 24 months was 61.4% (95% confidence interval [CI], 46.3 to 73.4) in the dostarlimab group and 15.7% (95% CI, 7.2 to 27.0) in the placebo group (hazard ratio for progression or death, 0.28; 95% CI, 0.16 to 0.50; P<0.001). In the overall population, progression-free survival at 24 months was 36.1% (95% CI, 29.3 to 42.9) in the dostarlimab group and 18.1% (95% CI, 13.0 to 23.9) in the placebo group (hazard ratio, 0.64; 95% CI, 0.51 to 0.80; P<0.001). Overall survival at 24 months was 71.3% (95% CI, 64.5 to 77.1) with dostarlimab and 56.0% (95% CI, 48.9 to 62.5) with placebo (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.87). The most common adverse events that occurred or worsened during treatment were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group than in the placebo group., Conclusions: Dostarlimab plus carboplatin-paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR-MSI-H population. (Funded by GSK; RUBY ClinicalTrials.gov number, NCT03981796.)., (Copyright © 2023 Massachusetts Medical Society.)
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- 2023
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22. Immunotherapy in endometrial cancer.
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Mahdi H, Chelariu-Raicu A, and Slomovitz BM
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- Humans, Female, Microsatellite Instability, Immunotherapy, Microsatellite Repeats, Immune Checkpoint Inhibitors therapeutic use, Endometrial Neoplasms therapy
- Abstract
The Cancer Genome Atlas (TCGA) endometrial cancer data expanded our knowledge about the role of different immunotherapeutic approaches based on molecular subtypes. Immune checkpoint inhibitors demonstrated distinct antitumor activities as monotherapy or in combination. In microsatellite unstable (microsatellite instability-high) endometrial cancer, immunotherapy with immune checkpoint inhibitors showed promising single agent activity in recurrent settings. Different strategies are needed to enhance the response or reverse resistance to immune checkpoint inhibitors, or both, in microsatellite instability-high endometrial cancer. On the other hand, single immune checkpoint inhibitors showed underwhelming efficacy in microsatellite stable endometrial cancer but this was significantly improved using a combination approach. Furthermore, studies are also needed to improve response along with ensuring safety and tolerability in microsatellite stable endometrial cancer. This review summarizes the current indications of immunotherapy for the treatment of advanced and recurrent endometrial cancer. We also outline potential future strategies for an immunotherapy based combination approach in endometrial cancer to combat resistance or enhance response to immune checkpoint inhibitors, or both., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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23. Cediranib in Combination with Olaparib in Patients without a Germline BRCA1/2 Mutation and with Recurrent Platinum-Resistant Ovarian Cancer: Phase IIb CONCERTO Trial.
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Lee JM, Moore RG, Ghamande S, Park MS, Diaz JP, Chapman J, Kendrick J, Slomovitz BM, Tewari KS, Lowe ES, Milenkova T, Kumar S, Dymond M, Brown J, and Liu JF
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- Adolescent, Adult, BRCA1 Protein genetics, Bevacizumab adverse effects, Carcinoma, Ovarian Epithelial drug therapy, Carcinoma, Ovarian Epithelial genetics, Female, Germ Cells, Germ-Line Mutation, Humans, Indoles, Mutation, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local genetics, Phthalazines, Piperazines, Quinazolines, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics, Poly(ADP-ribose) Polymerase Inhibitors adverse effects
- Abstract
Purpose: The efficacy, safety, and tolerability of cediranib plus olaparib (cedi/ola) were investigated in patients with nongermline-BRCA-mutated (non-gBRCAm) platinum-resistant recurrent ovarian cancer., Patients and Methods: PARP inhibitor-naïve women aged ≥18 years with platinum-resistant non-gBRCAm ovarian cancer, ECOG performance status of 0-2, and ≥3 prior lines of therapy received cediranib 30 mg once daily plus olaparib 200 mg twice daily in this single-arm, multicenter, phase IIb trial. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using RECIST 1.1. Progression-free survival (PFS), overall survival (OS), and safety and tolerability were also examined., Results: Sixty patients received cedi/ola, all of whom had confirmed non-gBRCAm status. Patients had received a median of four lines of chemotherapy; most (88.3%) had received prior bevacizumab. ORR by ICR was 15.3%, median PFS was 5.1 months, and median OS was 13.2 months. Forty-four (73.3%) patients reported a grade ≥3 adverse event (AE), with one patient experiencing a grade 5 AE (sepsis), considered unrelated to the study treatment. Dose interruptions, reductions, and discontinuations due to AEs occurred in 55.0%, 18.3%, and 18.3% of patients, respectively. Patients with high global loss of heterozygosity (gLOH) had ORR of 26.7% [4/15; 95% confidence interval (CI), 7.8-55.1], while ORR was 12.5% (4/32; 95% CI, 3.5-29.0) in the low gLOH group., Conclusions: Clinical activity was shown for the cedi/ola combination in heavily pretreated, non-gBRCAm, platinum-resistant patients with ovarian cancer despite failing to meet the target ORR of 20%, highlighting a need for further biomarker studies., (©2022 The Authors; Published by the American Association for Cancer Research.)
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- 2022
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24. Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe.
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Van der Kolk WL, Van der Zee AGJ, Slomovitz BM, Baldwin PJW, Van Doorn HC, De Hullu JA, Van der Velden J, Gaarenstroom KN, Slangen BFM, Kjolhede P, Brännström M, Vergote I, Holland CM, Coleman R, Van Dorst EBL, Van Driel WJ, Nunns D, Widschwendter M, Nugent D, DiSilvestro PA, Mannel RS, Tjiong MY, Boll D, Cibula D, Covens A, Provencher D, Runnebaum IB, Monk BJ, Zanagnolo V, Tamussino K, and Oonk MHM
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- Female, Groin, Humans, Lymph Node Excision adverse effects, Lymph Nodes pathology, Lymph Nodes surgery, Lymphatic Metastasis pathology, Neoplasm Recurrence, Local pathology, Sentinel Lymph Node Biopsy, Carcinoma, Squamous Cell pathology, Lymphadenopathy pathology, Sentinel Lymph Node pathology, Sentinel Lymph Node surgery, Vulvar Neoplasms pathology
- Abstract
Objective: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN., Methods: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up., Results: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence., Conclusion: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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25. Efficacy of niraparib by time of surgery and postoperative residual disease status: A post hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study.
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O'Cearbhaill RE, Pérez-Fidalgo JA, Monk BJ, Tusquets I, McCormick C, Fuentes J, Moore RG, Vulsteke C, Shahin MS, Forget F, Bradley WH, Hietanen S, O'Malley DM, Dørum A, Slomovitz BM, Baumann K, Selle F, Calvert PM, Artioli G, Levy T, Kumar A, Malinowska IA, Li Y, Gupta D, and González-Martín A
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- Carcinoma, Ovarian Epithelial drug therapy, Carcinoma, Ovarian Epithelial surgery, Chemotherapy, Adjuvant, Cytoreduction Surgical Procedures, Female, Humans, Indazoles therapeutic use, Neoadjuvant Therapy, Neoplasm Staging, Neoplasm, Residual, Piperidines, Ovarian Neoplasms drug therapy, Ovarian Neoplasms pathology, Ovarian Neoplasms surgery
- Abstract
Objective: To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence., Methods: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual disease [VRD]) in the intent-to-treat population., Results: In PRIMA (N = 733), 236 (32.2%) patients underwent PDS, and 481 (65.6%) received NACT/IDS before enrollment. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) for progression were similar in PDS (13.7 vs 8.2 months; HR, 0.67 [0.47-0.96]) and NACT/IDS (14.2 vs 8.2 months; HR, 0.57 [0.44-0.73]) subgroups. In patients who received NACT/IDS and had NVRD (n = 304), the hazard ratio (95% CI) for progression was 0.65 (0.46-0.91). In patients with VRD following PDS (n = 183) or NACT/IDS (n = 149), the hazard ratios (95% CI) for progression were 0.58 (0.39-0.86) and 0.41 (0.27-0.62), respectively. PFS was not evaluable for patients with PDS and NVRD because of sample size (n = 37)., Conclusions: In this post hoc analysis, niraparib efficacy was similar across PDS and NACT/IDS subgroups. Patients who had NACT/IDS and VRD had the highest reduction in the risk of progression with niraparib maintenance., Competing Interests: Declaration of Competing Interest REO reports participating in advisory boards with Bayer, Fresenius Kabi, GlaxoSmithKline, Immunogen, Regeneron, and Seattle Genetics; personal fees from GOG Foundation; and service as a noncompensated steering committee member for the PRIMA (niraparib) and DUO-O (olaparib) studies; institutional research support grants from AstraZeneca/Merck, Atara Biotherapeutics/Bayer, Genentech, Genmab, GlaxoSmithKline, Gynecologic Oncology Group Foundation, Juno Therapeutics, Kite/Gilead, Ludwig Institute for Cancer Research, Regeneron, Sellas Life Sciences, Stem CentRx, Syndax, TapImmune Inc., and TCR2 Therapeutics. JAPF reports personal fees from Abilify Pharma, Amgen, AstraZeneca, Clinigen, Clovis, GlaxoSmithKline, and Roche; and institutional grants from GlaxoSmithKline. BJM reports consulting fees from Agenus, Akeso Bio, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Macrogenics, Mersana, Myriad, Novartis, Novocure, Regeneron, Sorrento, Pfizer, Puma, US Oncology Research, and VBL; speaker's bureau honoraria from AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, TESARO/GSK; and is an investigator for US Oncology Research. IT reports personal fees from Celgene and Roche Pharma AG; institutional grants from Roche; and travel support from Roche. RGM reports personal fees from Abcodia Inc., Fujirebio Diagnostics Inc., and Humphries Pharmaceutical; and institutional grants from Angle Plc. MSS reports personal fees from AstraZeneca, Clovis Oncology, GlaxoSmithKline, Merck, and Pacira Pharmaceuticals Inc.; and institutional grants from GlaxoSmithKline. DO reports personal fees from Agenus, Eisai, GlaxoSmithKline, and Immunogen; consultant/advisory board for Abbvie, Ambry, Amgen, Array Biopharma, Clovis, EMD Serono, Ergomed, Janssen/J&J, INC Research Inc., inVentiv Health Clinical, Iovance Biotherapeutics Inc., Myriad Genetics, Novacure, Regeneron, Tarveda, and VentiRx; steering committee for Genentech/Roche and Merck; institutional funding from Ajinomoto Inc., Bristol Myers Squibb, Cerulean Pharma, GOG Foundation, Ludwig Cancer Research, New Mexico Cancer Care Alliance, PRA International, Stemcentrx Inc., Serono Inc., Tracon Pharmaceuticals, and Yale University. BMS reports consulting/advisory fees from Abbvie, AstraZeneca, Clovis, Eisai, Genentech, GlaxoSmithKline, GOG Foundation, Merck, and Myriad. FS reports personal fees from AstraZeneca, Clovis, GlaxoSmithKline, MSD, PharmaMar, and Roche; and travel support from AstraZeneca, GlaxoSmithKline, MSD, PharmaMar, and Roche. AK reports personal fees from AstraZeneca and GlaxoSmithKline. AGM reports consulting or advisory roles at Amgen, AstraZeneca, Clovis, Genmab, GlaxoSmithKline, Merck & Co., Mersana, Immunogen, Roche, Sotio, and Takeda; speaker's bureau compensation from AstraZeneca, Clovis, GlaxoSmithKline, Merck & Co., and Roche; institutional research funding from Roche and GlaxoSmithKline; and travel support from AstraZeneca, GlaxoSmithKline, and Roche. CM, CV, JF, FF, WHB, SH, AD, KB, PMC, GA, and TL have nothing to disclose. IAM and DG are employees of GlaxoSmithKline. YL was an employee at GlaxoSmithKline at the time of the analysis; currently an employee of Adagio Therapeutics Inc., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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26. The vaginal microbiome is associated with endometrial cancer grade and histology.
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Hakimjavadi H, George SH, Taub M, Dodds LV, Sanchez-Covarrubias AP, Huang M, Pearson JM, Slomovitz BM, Kobetz EN, Gharaibeh R, Sowamber R, Pinto A, Chamala S, and Schlumbrecht MP
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- Humans, Female, Vagina microbiology, Hysterectomy, Endometrial Neoplasms genetics, Microbiota genetics, Carcinoma
- Abstract
The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications., Competing Interests: Disclosure/Conflict of Interest: The authors declare no potential conflicts of interest.
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- 2022
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27. A randomized phase II trial of everolimus and letrozole or hormonal therapy in women with advanced, persistent or recurrent endometrial carcinoma: A GOG Foundation study.
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Slomovitz BM, Filiaci VL, Walker JL, Taub MC, Finkelstein KA, Moroney JW, Fleury AC, Muller CY, Holman LL, Copeland LJ, Miller DS, and Coleman RL
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- Drug Combinations, Estradiol, Estriol, Estrone, Everolimus therapeutic use, Female, Humans, Letrozole therapeutic use, Phosphatidylinositol 3-Kinases, Antineoplastic Combined Chemotherapy Protocols adverse effects, Endometrial Neoplasms drug therapy, Endometrial Neoplasms pathology, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology
- Abstract
Background: Blocking the PI3K/AKT/mTOR pathway decreases resistance to hormonal therapy in endometrial carcinoma (EC)., Objective: In this study, the aim was to assess the efficacy and tolerability of everolimus(E)/letrozole (L) or medroxyprogesterone acetate(M)/tamoxifen(T) in the treatment of metastatic EC., Study Design: This single stage, open-label two arm randomized phase II trial accrued women with advanced/persistent/recurrent EC. Treatment with E (10 mg daily) and L (2.5 mg daily) or T (20 mg twice daily) and M (200 mg daily alternating weeks) was randomly assigned, and stratified by prior adjuvant therapy. Treatments were administered orally. Primary endpoint was response rate., Results: Between February 2015 and April 2016, everolimus/letrozole (n = 37) or MT (n = 37) was assigned to 74 patients. Median follow-up was 37 months. Eight (22%; 95% CI 11% to 37%) patients responded on EL (one CR) and nine (25%; 95% CI 14% to 41%) patients responded on MT (three CRs). Median PFS for EL and MT arms was 6 months and 4 months, respectively. On EL, chemo-nave patients demonstrated a 28 month median PFS; prior chemotherapy patients had a 4-month median PFS. On MT, patients without prior therapy had a 5-month median PFS; those with prior chemotherapy demonstrated a 3-month PFS. Common grade 3 adverse events were anemia (9 [24%] patients EL vs 2 [6%] MT) and mucositis (2 [5%] vs 0 [0%]). Grade 3/4 thromboembolic events were observed with MT but not with EL (0 [0%] vs 4 [11%])., Conclusions: EL and MT demonstrated clinically meaningful efficacy in recurrent EC patients. The higher PFS observed in chemo-naïve patients is worthy of confirmation in future studies., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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28. Phase II Study of Taselisib in PIK3CA -Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I.
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Krop IE, Jegede OA, Grilley-Olson JE, Lauring JD, Mitchell EP, Zwiebel JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Kono SA, Ford JM, Garcia AA, Sui XD, Siegel RD, Slomovitz BM, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, and Flaherty KT
- Subjects
- Class I Phosphatidylinositol 3-Kinases genetics, Humans, Imidazoles, National Cancer Institute (U.S.), Oxazepines, Phosphatidylinositol 3-Kinases genetics, United States, Carcinoma, Squamous Cell drug therapy, Lung Neoplasms drug therapy
- Abstract
Purpose: PIK3CA mutations frequently contribute to oncogenesis in solid tumors. Taselisib, a potent and selective inhibitor of phosphoinositide 3-kinase, has demonstrated clinical activity in PIK3CA -mutant breast cancer. Whether PIK3CA mutations predict sensitivity to taselisib in other cancer types is unknown. National Cancer Institute-Molecular Analysis for Therapy Choice Arm EAY131-I is a single-arm, phase II study of the safety and efficacy of taselisib in patients with advanced cancers., Methods: Eligible patients had tumors with an activating PIK3CA mutation. Patients with breast or squamous cell lung carcinoma, or whose cancer had KRAS or PTEN mutations, were excluded. Patients received taselisib 4 mg, orally once daily continuously, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included progression-free survival (PFS), 6-month PFS, overall survival (OS), and identification of predictive biomarkers., Results: Seventy patients were enrolled, and 61 were eligible and initiated protocol therapy. Types of PIK3CA mutations included helical 41 of 61 (67%), kinase 11 of 61 (18%), and other 9 of 61 (15%). With a median follow-up of 35.7 months, there were no complete or partial responses. Six-month PFS was 19.9% (90% CI, 12.0 to 29.3) and median PFS was 3.1 months (90% CI, 1.8 to 3.7). Six-month OS was 60.7% (90% CI, 49.6 to 70.0) and median OS was 7.2 months (90% CI, 5.9 to 10.0). Individual comutations were too heterogeneous to correlate with clinical outcome. Fatigue, diarrhea, nausea, and hyperglycemia were the most common toxicities, and most were grade 1 and 2., Conclusion: In this study, taselisib monotherapy had very limited activity in a heterogeneous cohort of heavily pretreated cancer patients with PIK3CA -mutated tumors; the presence of a PIK3CA mutation alone does not appear to be a sufficient predictor of taselisib activity., Competing Interests: Ian E. KropEmployment: Freeline Therapeutics (I), PureTech (I), AMAG Pharmaceuticals (I)Leadership: AMAG Pharmaceuticals (I), Freeline Therapeutics (I), PureTech (I)Stock and Other Ownership Interests: AMAG Pharmaceuticals (I), Freeline Therapeutics (I), PureTech (I)Honoraria: Genentech/Roche, AstraZeneca, CelltrionConsulting or Advisory Role: Genentech/Roche, Seattle Genetics, Daiichi Sankyo, Macrogenics, Novartis, Merck, Bristol Myers Squibb, AstraZenecaResearch Funding: Genentech (Inst), Pfizer (Inst) Juneko E. Grilley-OlsonConsulting or Advisory Role: Bayer, Chimerix, Kura Oncology, SpringWorks TherapeuticsResearch Funding: NanoCarrier (Inst), Genentech (Inst), Seattle Genetics (Inst), Pfizer (Inst), Loxo (Inst), Astellas Pharma (Inst), Iovance Biotherapeutics (Inst) Josh D. LauringEmployment: Janssen Research & DevelopmentStock and Other Ownership Interests: Johnson & JohnsonConsulting or Advisory Role: Galderma (I), Regeneron (I), Novartis (I)Speakers' Bureau: Galderma (I), AbbVie (I), Pfizer (I)Patents, Royalties, Other Intellectual Property: I intermittently receive royalty payments for cell lines created in my laboratory, which are licensed for commercial sale to Horizon Discovery, Ltd by Johns Hopkins UniversityTravel, Accommodations, Expenses: Galderma (I), AbbVie (I) Edith P. MitchellLeadership: Corvus PharmaceuticalsHonoraria: Sanofi, ExelixisConsulting or Advisory Role: Genentech, Novartis, Merck, Bristol Myers SquibSpeakers' Bureau: IpsenResearch Funding: Genentech (Inst), sanofi (Inst) Robert J. GrayResearch Funding: Agios, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Genentech/Roche, Genomic Health, Genzyme, GlaxoSmithKline, Janssen-Ortho, Onyx, Pfizer, Sequenta, Syndax, Novartis, Takeda, AbbVie, Sanofi, Merck Sharp & Dohme P. Mickey WilliamsResearch Funding: Illumina (Inst)Patents, Royalties, Other Intellectual Property: I was a coinventor of the DLBCL cell of origin patent recently filed by the NIH Stanley R. HamiltonResearch Funding: Minerva Biotechnologies, Intima James M. FordThis author is the Editor-in-Chief for JCO Precision Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.Research Funding: Genentech (Inst), AstraZeneca (Inst), Puma Biotechnology (Inst), Pfizer (Inst), Merus (Inst), Bayer (Inst), Incyte (Inst) Agustin A. GarciaConsulting or Advisory Role: Biotheranostics, GlaxoSmithKlineResearch Funding: Advenchen Laboratories (Inst), Seattle Genetics (Inst), Merck (Inst), Iovance Pharm (Inst) Xingwei D. SuiConsulting or Advisory Role: Novartis Robert D. SiegelResearch Funding: Merck (Inst), Mirati Therapeutics (Inst), GRAIL (Inst), Altor BioScience (Inst), Galera Therapeutics (Inst), Apollomics (Inst), Strata Oncology (Inst), Arcus Biosciences (Inst), Bristol Myers Squibb (Inst), Cancer Insight (Inst), Puma Biotechnology (Inst), Conjupro Biotherapeutics (Inst), Razor Genomics (Inst), Sanofi (Inst), Seattle Genetics (Inst)Other Relationship: American Board of Internal Medicine (ABIM) Brian M. SlomovitzConsulting or Advisory Role: Clovis Oncology, AstraZeneca, Genentech, Incyte, Agenus, GlaxoSmithKline, GOG Foundation, Myriad Genetics, Merck, Eisai Carlos L. ArteagaStock and Other Ownership Interests: Provista DiagnosticsConsulting or Advisory Role: Novartis, Lilly, Sanofi, Radius Health, Taiho Pharmaceutical, Puma Biotechnology, Merck, Origimed, Immunomedics, Daiichi Sankyo, Athenex, Astrazeneca, ArvinasResearch Funding: Pfizer, Lilly, TakedaOther Relationship: Susan G. Komen for the Cure Lyndsay N. HarrisPatents, Royalties, Other Intellectual Property: Philips Healthcare Peter J. O'DwyerConsulting or Advisory Role: GenentechResearch Funding: Bristol Myers Squibb (Inst), Pfizer (Inst), Novartis (Inst), Genentech (Inst), Mirati Therapeutics (Inst), Celgene (Inst), GlaxoSmithKline (Inst), BBI Healthcare (Inst), Pharmacyclics (Inst), Five Prime Therapeutics (Inst), Forty Seven (Inst), Amgen (Inst), H3 Biomedicine (Inst), Taiho Pharmaceutical (Inst), Array BioPharma (Inst), Lilly/ImClone (Inst), Syndax (Inst), Syndax (Inst), Syndax (Inst), Syndax (Inst), syndax (Inst), Minneamrita Therapeutics (Inst)Expert Testimony: Lilly, Dai-ichi Sankyo Alice P. Chen(OPTIONAL) Uncompensated Relationships: Frontiers in Medicine Keith T. FlahertyStock and Other Ownership Interests: Clovis Oncology, Loxo, X4 Pharma, Strata Oncology, PIC Therapeutics, Shattuck Labs, Apricity Health, Oncoceutics, FOGPharma, Tvardi Therapeutics, Checkmate Pharmaceuticals, Kinnate Biopharma, Scorpion Therapeutics, ALX Oncology, xCures, Monopteros Therapeutics, Vibliome Therapeutics, Transcode Therapeutics, Soley TherapeuticsConsulting or Advisory Role: Novartis, Lilly, Oncoceutics, Tvardi Therapeutics, Takeda, Boston Biomedical, Debiopharm Group, FOGPharmaNo other potential conflicts of interest were reported.
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- 2022
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29. Changing treatments paradigms and role of immunotherapy in recurrent endometrial cancer.
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Chelariu-Raicu A, Mahdi H, and Slomovitz BM
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- Female, Humans, Immunotherapy, Microsatellite Instability, Endometrial Neoplasms drug therapy, Endometrial Neoplasms genetics, Neoplasm Recurrence, Local therapy
- Abstract
Purpose of Review: Over the past decade, the treatment of patients diagnosed with endometrial cancer (EC) shifted away from the use of chemotherapy to more novel targeted therapy and immunotherapy approaches., Recent Findings: The Cancer Genome Atlas data demonstrated different subgroups within ECs, more specifically, it facilitated the identification of predictive biomarkers. In particular, immunotherapies (immuno-oncology (IO)) are active either as monotherapy or in combination with other agents, depending on the biomarker profile of the tumor., Summary: In May 2017, pembrolizumab was approved for patients with microsatellite instability high (MSI-H) EC. More recently, this approval was extended for patients harvesting tumors with a high tumor mutational burden status. Furthermore, in July 2021, the combination of pembrolizumab and lenvatinib was approved for patients who do not exhibit MSI-H disease. Given the wealth of targets in EC and different targetable mutations, the challenge will be to choose the proper treatment and the proper sequencing to derive the best outcome in the first-line setting and improve outcomes in subsequent settings. This review summarizes the current indications of immunotherapy for the treatment of advanced and recurrent EC. We outline the role of testing for uterine cancer and its implication in therapy management. Finally, we address new concepts for immunotherapy combinations with other therapies., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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30. RaPiDS (GOG-3028): randomized Phase II study of balstilimab alone or in combination with zalifrelimab in cervical cancer.
- Author
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O'Malley DM, Randall LM, Jackson CG, Coleman RL, Hays JL, Moore KN, Naumann RW, Rocconi RP, Slomovitz BM, Tewari KS, Ancukiewicz M, Feliu WO, and Monk BJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Middle Aged, Prognosis, Uterine Cervical Neoplasms immunology, Uterine Cervical Neoplasms pathology, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Clinical Trials, Phase II as Topic methods, Immune Checkpoint Inhibitors therapeutic use, Randomized Controlled Trials as Topic methods, Uterine Cervical Neoplasms drug therapy
- Abstract
Balstilimab (anti-programmed death 1) and zalifrelimab (anti-CTLA-4) are two new checkpoint inhibitors that have emerged as promising investigational agents for the treatment of cervical cancer, particularly in the setting of previously-treated, recurrent/metastatic disease. Here we describe the rationale and design of RaPiDS (NCT03894215), a two-arm Phase II study evaluating the safety, tolerability and efficacy of balstilimab administered alone or in combination with zalifrelimab in patients with advanced cervical cancer who progressed after first-line, platinum-based chemotherapy. Patients will be randomized in a 1:1 ratio. The primary end point is objective response rate, and key secondary objectives include safety, duration of response, progression-free survival, overall survival and quality of life outcomes.
- Published
- 2021
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31. Uterine carcinosarcomas: From pathology to practice.
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Toboni MD, Crane EK, Brown J, Shushkevich A, Chiang S, Slomovitz BM, Levine DA, Dowdy SC, Klopp A, Powell MA, and Thaker PH
- Subjects
- Combined Modality Therapy, Female, Humans, Carcinosarcoma pathology, Carcinosarcoma therapy, Uterine Neoplasms pathology, Uterine Neoplasms therapy
- Abstract
Objective: Uterine carcinosarcoma (UCS) is a rare but aggressive cancer. In early-stage disease data guiding treatment is sparse. The purpose of this review is to summarize the findings from the 2019 NRG oncology group summer symposium meeting as well as a review of the current literature, with a particular focus on molecular targets, ongoing clinical trials, and treatment of early and advanced/recurrent disease., Methods: A combination of expert presentations and an extensive literature search was undertaken to summarize the literature in this review. MEDLINE was queried for peer-reviewed publications on UCS. This search was not limited by year or study design, but was limited to English language publications. ClinicalTrials.gov was queried for ongoing trials in UCS., Results: UCS is a rare cancer that is biphasic, with the carcinomatous component driving its aggressive nature. Level 3 evidence regarding early stage disease is lacking, but retrospective data suggests adjuvant therapy is warranted. The recent results of GOG 261 have contributed valuable information towards treatment strategy, including use of paclitaxel and carboplatin for UCS. Clinical trials are ongoing to investigate new targeted agents in UCS., Conclusion: Ongoing endometrial cancer clinical trials now include UCS patients. In combination with advances in molecular profiling, this will provide patients with UCS improved therapeutic options. Until that time, surgical resection and traditional cytotoxic chemotherapy remains standard of care., Competing Interests: Declaration of Competing Interest The authors report no conflicts related to the creation of this manuscript. Individual COIs are submitted for each auther., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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32. The GOG partners: A program for industry sponsored clinical trials in gynecologic oncology within the GOG foundation.
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Monk BJ, Coleman RL, Herzog TJ, Moore KN, O'Malley DM, Randall LM, Slomovitz BM, Eskander R, Pothuri B, Reese LL, Mannel RS, and Copeland LJ
- Subjects
- Clinical Trials as Topic methods, Female, Humans, Randomized Controlled Trials as Topic, Clinical Trials as Topic organization & administration, Drug Industry organization & administration, Genital Neoplasms, Female therapy, Gynecology organization & administration, Medical Oncology organization & administration
- Abstract
The GOG Foundation, Inc. (GOG-F) is a non-profit 501(c)(3) organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies. GOG Partners (GOG-P) is a program of the GOG-F and is positioned alongside NRG Oncology under the GOG-F organizational umbrella. GOG-P operates outside of the federally funded NCI NRG Oncology, a key distinguishing feature. By functioning as a site management organization (SMO), GOG-P provides an additional platform for clinical trial development, mentorship opportunities, patient accrual, and site infrastructure support yielding an expanded gynecologic oncology clinical trials infrastructure in the US. GOG-P has a consistent track record of conducting high quality clinical trials that lead to bringing novel FDA approved treatments for gynecologic cancer. This manuscript summarizes the history and organizational structure of the GOG-P. In addition, we outline the other key supportive programs within the GOG-F that help support the GOG-P effort to perform transformative gynecologic cancer research., Competing Interests: Declaration of Competing Interest Dr. Coleman reports grants and personal fees from AstraZeneca, grants from Merck, personal fees from GSK, grants and personal fees from Clovis, grants and personal fees from Genmab, grants and personal fees from Roche/Genentech, grants and personal fees from Janssen, personal fees from Agenus, personal fees from Regeneron, personal fees from OncoQuest, outside the submitted work., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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33. Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial.
- Author
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Rocconi RP, Grosen EA, Ghamande SA, Chan JK, Barve MA, Oh J, Tewari D, Morris PC, Stevens EE, Bottsford-Miller JN, Tang M, Aaron P, Stanbery L, Horvath S, Wallraven G, Bognar E, Manning L, Nemunaitis J, Shanahan D, Slomovitz BM, Herzog TJ, Monk BJ, and Coleman RL
- Subjects
- Aged, Cancer Vaccines adverse effects, Carcinoma, Endometrioid immunology, Carcinoma, Endometrioid pathology, Double-Blind Method, Female, Humans, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Ovarian Neoplasms immunology, Ovarian Neoplasms mortality, Ovarian Neoplasms pathology, Time Factors, Treatment Outcome, United States, Cancer Vaccines administration & dosage, Carcinoma, Endometrioid therapy, Ovarian Neoplasms therapy
- Abstract
Background: Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-β1 and TGF-β2. The aim of this study was to determine the safety and efficacy of gemogenovatucel-T in front-line ovarian cancer maintenance., Methods: This randomised, double-blind, placebo-controlled, phase 2b trial involved 25 hospitals in the USA. Women aged 18 years and older with stage III/IV high-grade serous, endometrioid, or clear cell ovarian cancer in clinical complete response after a combination of surgery and five to eight cycles of chemotherapy involving carboplatin and paclitaxel, and an Eastern Cooperative Oncology Group status of 0 or 1 were eligible for inclusion in the study. Patients were randomly assigned (1:1) to gemogenovatucel-T or placebo by an independent third party interactive response system after successful screening using randomly permuted block sizes of two and four and stratified by extent of surgical cytoreduction and neoadjuvant versus adjuvant chemotherapy. Gemogenovatucel-T (1 × 10
7 cells per injection) or placebo was administered intradermally (one per month) for a minimum of four and up to 12 doses. Patients, investigators, and clinical staff were masked to patient allocation until after statistical analysis. The primary endpoint was recurrence-free survival, analysed in the per-protocol population. All patients who received at least one dose of gemogenovatucel-T were included in the safety analysis. The study is registered with ClinicalTrials.gov, NCT02346747., Findings: Between Feb 11, 2015, and March 2, 2017, 310 patients consented to the study at 22 sites. 217 were excluded. 91 patients received gemogenovatucel-T (n=47) or placebo (n=44) and were analysed for safety and efficacy. The median follow-up from first dose of gemogenovatucel-T was 40·0 months (IQR 35·0-44·8) and from first dose of placebo was 39·8 months (35·5-44·6). Recurrence-free survival was 11·5 months (95% CI 7·5-not reached) for patients assigned to gemogenovatucel-T versus 8·4 months (7·9-15·5) for patients assigned to placebo (HR 0·69, 90% CI 0·44-1·07; one-sided p=0·078). Gemogenovatucel-T resulted in no grade 3 or 4 toxic effects. Two patients in the placebo group had five grade 3 toxic events, including arthralgia, bone pain, generalised muscle weakness, syncope, and dyspnea. Seven patients (four in the placebo group and three in the gemogenovatucel-T group) had 11 serious adverse events. No treatment-related deaths were reported in either of the groups., Interpretation: Front-line use of gemogenovatucel-T immunotherapy as maintenance was well tolerated but the primary endpoint was not met. Further investigation of gemogenovatucel-T in patients stratified by BRCA mutation status is warranted., Funding: Gradalis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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34. Phase Ib/II study of weekly topotecan and daily gefitinib in patients with platinum resistant ovarian, peritoneal, or fallopian tube cancer.
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Chelariu-Raicu A, Levenback CF, Slomovitz BM, Wolf J, Bodurka DC, Kavanagh JJ, Morrison C, Gershenson DM, and Coleman RL
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Drug Administration Schedule, Drug Resistance, Neoplasm, ErbB Receptors drug effects, Female, Gefitinib adverse effects, Humans, Middle Aged, Neoplasm Recurrence, Local drug therapy, Prospective Studies, Protein Kinase Inhibitors adverse effects, Topoisomerase I Inhibitors adverse effects, Topotecan adverse effects, Carcinoma, Ovarian Epithelial drug therapy, Fallopian Tube Neoplasms drug therapy, Gefitinib administration & dosage, Protein Kinase Inhibitors administration & dosage, Topoisomerase I Inhibitors administration & dosage, Topotecan administration & dosage
- Abstract
Introduction: 50-70% of epithelial ovarian cancers overexpress epidermal growth factor receptor, and its expression has been correlated with poor prognosis. We conducted a phase Ib/II trial to examine the efficacy, safety, and toxicity of gefitinib, a tyrosine kinase inhibitor, combined with topotecan in women with recurrent ovarian cancer with epidermal growth factor receptor positivity., Methods: Patients with measurable recurrent or persistent cancer after treatment with a platinum containing regimen with positive epidermal growth factor receptor expression, as determined by immunohistochemistry, were eligible for the study. Initial treatment was 250 mg/day gefitinib (oral) and 2.0 mg/m
2 topotecan (intravenous) on days 1, 8, and 15, on a 28 day cycle. Dose escalations were planned for topotecan (dose levels 1-3: 2, 3, and 4 mg/m2 ) until the maximum tolerated dose was reached., Results: 19 patients received a total of 61 cycles. Median age was 59.8 years (range 42-76 years). Histologic types in treated patients included 74% serous (n=14), 11% mixed (n=2), 11% transitional (n=2), and 5% clear cell (n=1). For phase Ib, three patients were treated at dose level 1, three at dose level 2, and three at dose level 3 for topotecan. The maximum tolerated dose was 4.0 mg/m2 (days 1, 8, and 15) for topotecan and 250 mg (daily) for gefitinib. Therefore, dose level 3 was used for phase II. Among the 19 patients, 63.2% (n=12) had progressive disease, 15.8% (n=3) had stable disease, 10.5% (n=2) had a partial response, and 10.5% (n=2) were not evaluable. The most serious adverse events of any grade attributed to the therapy were anemia (89.4%), neutropenia (68.4%), abdominal pain (84%), constipation (78.9%), and diarrhea (78.9%)., Conclusion: Although the drug combination was relatively well tolerated, this prospective phase Ib/II clinical trial did not show sufficient clinical activity of topotecan combined with gefitinib in patients with epidermal growth factor receptor positive recurrent ovarian, fallopian tube, or peritoneal cancers., Competing Interests: Competing interests: BMS is consultant for Abbvie, AstraZeneca, Clovis, GOG Foundation, GSK, Merck, and Myriad. DCB receives research grants from the National Cancer Institute. DMG has equity interest in Biogen, Bristol Myers Squibb, Johnson & Johnson, Procter and Gamble; is a consultant for Genentech; received research grants from the National Cancer Institute and Novartis; received royalities from Elsevier and UpToDate; and is a board member of NCI Clinical Trials and Translational Research Advisory Committee. RLC has clinical research funding from Merck, AstraZeneca/Medimmune, Genentech/Roche, Novartis, Clovis Oncology, Abbvie, and Janssen Pharmaceuticals. RLC receives consulting fees from Genmab, Tesaro, Agenus, OncoMed, Novocure, Oncoquest, Merck, AstraZeneca/Medimmune, Genentech/Roche, Novartis, Clovis Oncology, Abbvie, Janssen Pharmaceuticals, Aravive, and OncoSec., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2020
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35. Phase 2 study of cetuximab (Erbitux) in patients with progressive or recurrent endometrial cancer.
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Slomovitz BM, Chelariu-Raicu A, Schmeler KM, Lu KH, Gershenson DM, Wolf J, and Coleman RL
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological adverse effects, Cetuximab adverse effects, ErbB Receptors, Female, Humans, Middle Aged, Antineoplastic Agents, Immunological administration & dosage, Cetuximab administration & dosage, Endometrial Neoplasms drug therapy, Neoplasm Recurrence, Local drug therapy
- Abstract
Introduction: Overexpression of the epidermal growth factor receptor (EGFR) found in common subtypes of endometrial cancer has been associated with advanced stage disease and a poor prognosis. The purpose of this phase 2 study was to evaluate the efficacy and safety of cetuximab in patients with recurrent endometrial cancer., Methods: The study was an open-label phase 2 clinical trial conducted at two institutions. Patients with recurrent or progressive endometrial cancer of any histologic type with the exception of uterine sarcoma received cetuximab at an initial dose of 400 mg/m
2 IV followed by weekly doses of 250 mg/m2 . One cycle was considered 4 weeks of treatment. The primary efficacy endpoint was clinical benefit response, defined as a complete or partial response or prolonged stable disease (>8 weeks) by RECIST 1.0 criteria., Results: A total of 30 patients were enrolled with a median age of 64 years (range 42-83). Of the 20 evaluable patients, three (15%) had clinical benefit response (one complete response, two stable disease). The patient with a clinical benefit response received a total of 27 cycles and the two patients with stable disease were taken off the study due to progression after four and six cycles, respectively. Of the 10 inevaluable patients, nine received ≤1 cycle due to clinical deterioration and one had an anaphylactic reaction. One patient had a grade 3 rash which resolved after a delay in treatment. No dose reduction was reported., Conclusions: In this cohort, single agent therapy with cetuximab was well tolerated and had a 15% clinical benefit response. Further studies are required to better identify patients who may respond to this treatment., Competing Interests: Competing interests: BS: consultant for Abbvie, AstraZeneca, Clovis, GOG Foundation, GSK, Merck, Myriad. DG: Equity interest: Biogen, Bristol Myers Squibb, Johnson & Johnson, Procter and Gamble; Consulting: Genentech; Research grants: National Cancer Institute, Novartis; Royalities: Elsevier, UpToDate; Board Membership: NCI Clinical Trials and Translational Research Advisory Committee. RC: Clinical research funding: Merck, AstraZeneca/Medimmune, Genentech/Roche, Novartis, Clovis Oncology, Abbvie, and Janssen Pharmaceuticals; Consulting fees: Genmab, Tesaro, Agenus, OncoMed, Novocure, Oncoquest, Merck, AstraZeneca/Medimmune, Genentech/Roche, Novartis, Clovis Oncology, Abbvie, Janssen Pharmaceuticals, Aravive, OncoSec., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2020
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36. mRNA expression in low grade serous ovarian cancer: Results of a nanoString assay in a diverse population.
- Author
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Jordan SE, Saad H, Covarrubias AS, Siemon J, Pearson JM, Slomovitz BM, Huang M, Pinto A, Schlumbrecht M, and George SH
- Subjects
- Adult, Aged, Biomarkers, Tumor genetics, Cystadenocarcinoma, Serous ethnology, Cystadenocarcinoma, Serous pathology, Female, Gene Expression Profiling methods, Germ-Line Mutation, Humans, Middle Aged, Ovarian Neoplasms ethnology, Ovarian Neoplasms pathology, Progression-Free Survival, Proto-Oncogene Proteins p21(ras), Registries, Retrospective Studies, Tubulin, Xeroderma Pigmentosum Group D Protein, Young Adult, Cystadenocarcinoma, Serous genetics, Ovarian Neoplasms genetics, RNA, Messenger analysis
- Abstract
Objective: Mutations in the MAP kinase pathway (KRAS, NRAS, BRAF) are common in low grade serous ovarian carcinoma (LGSOC). The effect of these and other mutations on RNA transcription in this disease is poorly understood. Our objective was to describe patterns of somatic mutations and gene transcription in a racially diverse population with LGSOC., Methods: Utilizing an institutional tumor registry, patients with LGSOC were identified and charts were reviewed. RNA was extracted from available tumor tissue. Commercial tumor profiling results were analyzed with PanCancer pathway nanoString mRNA expression data. Along with nanoString n-Solver software, Chi-squared, Fishers Exact, and Cox proportional hazards models were used for statistical analysis, with significance set at p < 0.05., Results: 39 patients were identified-20% Black, 43% Hispanic, and 36% non-Hispanic White. 18 patients had commercial somatic DNA test results, and 23 had available tumor tissue for RNA extraction and nanoString analysis. The most common somatic alterations identified was KRAS (11 patients, 61%), followed by ERCC1 and TUBB3 (9 each, 50%). KRAS mutations were less common in smokers (14.3% vs 90.9%, p = 0.002). RNA expression analysis demonstrated a greater than two-fold decrease in expression of HRAS in tumors from older patients (p = 0.04), and a greater than two-fold decrease in the expression of HRAS in recurrent tumors (p = 0.007). No significant differences were seen in somatic testing results, RNA expression analysis, or progression free survival between different racial and ethnic cohorts., Conclusions: Somatic deficiencies in ERCC1, TUBB3, and KRAS are common in LGSOC in a population of minority patients. HRAS demonstrates decreased expression in tumors from older patients and recurrent tumors., Competing Interests: Declaration of Competing Interest BMS serves on advisory boards for GOG Foundation, Astra Zeneca, AbbVie, Clovis, GSK, Genentech, and Myriad. MH is supported in unrelated research by grants from Merck and Jansen, and serves on advisory boards for Clovis and GSK. The remaining authors have no relevant conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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37. State of the science: Uterine sarcomas: From pathology to practice.
- Author
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Shushkevich A, Thaker PH, Littell RD, Shah NA, Chiang S, Thornton K, Hensley ML, Slomovitz BM, Holcomb KM, Leitao MM, Toboni MD, Powell MA, Levine DA, Dowdy SC, Klopp A, and Brown J
- Subjects
- Adenosarcoma diagnosis, Adenosarcoma mortality, Adenosarcoma pathology, Antineoplastic Agents, Hormonal therapeutic use, Biomarkers, Tumor analysis, Biopsy, Carcinosarcoma diagnosis, Carcinosarcoma mortality, Carcinosarcoma pathology, Chemotherapy, Adjuvant standards, Disease-Free Survival, Endometrial Ablation Techniques, Female, Humans, Hysterectomy standards, Leiomyosarcoma diagnosis, Leiomyosarcoma mortality, Leiomyosarcoma pathology, Medical Oncology methods, Medical Oncology standards, Neoplasm Grading, Neoplasm Recurrence, Local epidemiology, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local prevention & control, Practice Guidelines as Topic, Prognosis, Radiotherapy, Adjuvant standards, Sarcoma, Endometrial Stromal diagnosis, Sarcoma, Endometrial Stromal mortality, Sarcoma, Endometrial Stromal pathology, Uterine Neoplasms diagnosis, Uterine Neoplasms mortality, Uterine Neoplasms pathology, Uterus diagnostic imaging, Uterus pathology, Uterus surgery, Adenosarcoma therapy, Carcinosarcoma therapy, Leiomyosarcoma therapy, Sarcoma, Endometrial Stromal therapy, Uterine Neoplasms therapy
- Abstract
Competing Interests: Declaration of Competing Interest Drs. Shushkevic, LIttell, Shah, Chiang, Thornton, Toboni. Levine, Dowdy and Klopp have nothing to disclose. Dr. Thaker reports grants and personal fees from Merck, personal fees from Stryker, personal fees from Celsion, personal fees from Astra Zeneca, grants and personal fees from GlaxoSmithKline, personal fees from Iovance, personal fees from Aravive, personal fees from Mersana, outside the submitted work. Dr. Hensley reports her spouse is an employee of Sanofi, and reports royalties from a chapter from Up To Date and honoraria from GSK and Tesaro. Dr. Slomovitz reports personal fees from Abbvie, AstraZeneca, Clovis, Genentech, GSK, Myriad, and Incyte; and research support from Novartis. Dr. Holcomb is a consultant for Johnson and Johnson and receives research support from Fujirebio Diagnostics. Neither relationship is relevant to the current manuscript. Dr. Leitao reports personal fees from JnJ/Ethicon, outside the submitted work; and Dr. Leitao is an ad hoc speaker for Intuitive Surgical, Inc. Dr. Powell reports consultant fees from Merck, Tesaro, AstraZeneca, Clovis, and Eisai, outside the submitted work. Dr. Brown reports personal fees from Clovis and GSK, outside the submitted work.
- Published
- 2020
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38. COVID-19 and ovarian cancer: Exploring alternatives to intravenous (IV) therapies.
- Author
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Monk BJ, Coleman RL, Moore KN, Herzog TJ, Secord AA, Matulonis UA, Slomovitz BM, Guntupalli SR, and O'Malley DM
- Subjects
- Administration, Oral, Betacoronavirus isolation & purification, COVID-19, Coronavirus Infections epidemiology, Coronavirus Infections virology, Female, Humans, Infusions, Intravenous, Organoplatinum Compounds administration & dosage, Pneumonia, Viral epidemiology, Pneumonia, Viral virology, SARS-CoV-2, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Coronavirus Infections prevention & control, Ovarian Neoplasms drug therapy, Ovarian Neoplasms virology, Pandemics prevention & control, Pneumonia, Viral prevention & control, Poly(ADP-ribose) Polymerase Inhibitors administration & dosage
- Abstract
Competing Interests: Declaration of competing interest Dr. Bradley J. Monk reports personal fees from AbbVie, personal fees from Advaxis, personal fees from Agenus, personal fees from Amgen, personal fees from Aravive, personal fees from AstraZeneca, personal fees from Asymmetric Therapeutics, personal fees from Boston Biomedical, personal fees from ChemoCare, personal fees from ChemoID, personal fees from Clovis Oncology, personal fees from Easai, personal fees from Geistlich, personal fees from Genmab/Seattle Genetics, personal fees from GOG Foundation, personal fees from ImmunoGen, personal fees from Immunomedics, personal fees from Incyte, personal fees from Janssen/Johnson & Johnson, personal fees from Laekna Health Care, personal fees from Mateon (formally Oxigene), personal fees from Merck, personal fees from Mersana, personal fees from Myriad, personal fees from Nucana, personal fees from Oncomed, personal fees from Oncoquest, personal fees from Oncosec, personal fees from Perthera, personal fees from Pfizer, personal fees from Precision Oncology, personal fees from Puma, personal fees from Regeneron, personal fees from Roche/Genentech, personal fees from Samumed, personal fees from Takeda, personal fees from Tesaro/GSK, personal fees from VBL, personal fees from Vigeo, personal fees from Iovance, personal fees from Vavotar Life Science, personal fees from Senti Bio, personal fees from Akesio Bio, personal fees from Dicepheria, personal fees from Tarveda, outside the submitted work. Dr. Robert L. Coleman reports other from US Oncology Research, during the conduct of the study; grants and personal fees from AstraZeneca, grants from Merck, personal fees from Tesaro, personal fees from Medivation, grants and personal fees from Clovis Oncology, personal fees from Gamamab, grants and personal fees from Genmab, grants and personal fees from Roche/Genentech, grants and personal fees from Janssen, personal fees from Agenus, personal fees from Regeneron, personal fees from OncoQuest, outside the submitted work. Dr. Thomas J, Herzog reports personal fees from Johnson & Johnson, personal fees from AstraZeneca, Caris, Clovis Oncology, Roche, and Tesaro. Dr. Kathleen Moore reports personal fees and other from Astra Zeneca, grants, personal fees and other from Genentech/Roche, grants, personal fees and other from Immunogen, grants, personal fees and other from Clovis Oncology, grants, personal fees and other from Tesaro, personal fees and other from Pfizer, personal fees from Janssen, personal fees from Aravive, personal fees from VBL Therapeutics, personal fees and other from Onco Med, personal fees from Samumed, grants and other from Lilly, personal fees from Eisai, personal fees from Vavotar, personal fees from Abbvie, personal fees from Tarveda, outside the submitted work. Dr. Thomas Herzog reports personal fees from Johnson & Johnson, personal fees from Clovis Oncology, personal fees from AstraZeneca, personal fees from GSK/Tesaro, personal fees from Roche, personal fees from Caris, personal fees from Abbvie, outside the submitted work. Dr. Angeles Alvarez Secord reports grants from AbbVie, Amgen, AstraZeneca, Clovis Oncology, Astellas Pharma Inc., Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Endocyte, Exelixis, Incyte, Merck, PharmaMar, Immutep Ltd., Roche/Genentech, Seattle Genetics, Inc., Tesaro/GSK, VBL Therapeutics, National Cancer Trial Network; honoraria from Aravive, AstraZeneca, Clovis Oncology, Cordgenics, Eisai, Janssen/Johnson & Johnson, Merck, Mersana, OncoQuest, Roche/Genentech, Tesaro/GSK Advisory Boards; participation on Clinical Trial Steering Committees (uncompensated) for Roche/Genentech, and VBL Therapeutics; and member of GOG-Foundation Board of Directors, outside the submitted work. Dr. Ursula A. Matulonis reports personal fees from AstraZeneca, Myriad Genetics, Clovis Oncology, Merck, Eli Lilly, Mersana, Geneos, Fuji Film, Cerulean, Immunogen, and 2× Oncology. Dr. Brian M. Slomovitz reports receiving consulting fees from AstraZeneca, Clovis Oncology, Incyte, Janssen, GSK/Tesaro, and Genentech/Roche. Dr. Saketh R. Guntupalli reports receiving consulting fees from AstraZeneca, Clovis Oncology, and Tesaro. Dr. David O'Malley reports personal fees and other from AstraZeneca, personal fees and other from Clovis Oncology, personal fees and other from Tesaro, personal fees and other from Immunogen, personal fees from Ambry, personal fees and other from Janssen/Johnson & Johnson, personal fees and other from Abbvie, personal fees and other from Regeneron, personal fees and other from Amgen, personal fees and other from Novocure, personal fees and other from Genentech/Roche, other from VentiRx, other from Array Biopharma, other from EMD Serono, other from Ergomed, other from Ajinomoto Inc., other from Ludwig Cancer Research, other from Stemcentrx, Inc., other from CERULEAN PHARMA, other from GOG Group, other from Bristol-Myers Squibb, other from Serono Inc., other from TRACON Pharmaceuticals, other from Yale University, other from New Mexico Cancer Care Alliance, other from INC Research, Inc., other from inVentiv Health Clinical, other from Iovance, other from PRA Intl, other from Agenus, outside the submitted work.
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- 2020
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39. Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer.
- Author
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Hong DS, Concin N, Vergote I, de Bono JS, Slomovitz BM, Drew Y, Arkenau HT, Machiels JP, Spicer JF, Jones R, Forster MD, Cornez N, Gennigens C, Johnson ML, Thistlethwaite FC, Rangwala RA, Ghatta S, Windfeld K, Harris JR, Lassen UN, and Coleman RL
- Subjects
- Adult, Aged, Carcinoma, Squamous Cell secondary, Female, Humans, Immunoconjugates therapeutic use, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local pathology, Patient Safety, Progression-Free Survival, Treatment Outcome, Uterine Cervical Neoplasms pathology, Young Adult, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Carcinoma, Squamous Cell drug therapy, Drug Resistance, Neoplasm, Neoplasm Recurrence, Local drug therapy, Oligopeptides therapeutic use, Uterine Cervical Neoplasms drug therapy
- Abstract
Purpose: Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody-drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623)., Patients and Methods: Patients with recurrent or metastatic cervical cancer received tisotumab vedotin 2.0 mg/kg every 3 weeks until progressive disease, unacceptable toxicity, or consent withdrawal. The primary objective was safety and tolerability. Secondary objectives included antitumor activity., Results: Of the 55 patients, 51% had received ≥2 prior lines of treatment in the recurrent or metastatic setting; 67% had prior bevacizumab + doublet chemotherapy. Fifty-one percent of patients had squamous cell carcinoma. The most common grade 3/4 treatment-emergent adverse events (AEs) were anemia (11%), fatigue (9%), and vomiting (7%). No grade 5 treatment-related AEs occurred. Investigator-assessed confirmed objective response rate (ORR) was 24% [95% confidence interval (CI): 13%-37%]. Median duration of response (DOR) was 4.2 months (range: 1.0
+ -9.7); four patients responded for >8 months. The 6-month progression-free survival (PFS) rate was 29% (95% CI: 17%-43%). Independent review outcomes were comparable, with confirmed ORR of 22% (95% CI: 12%-35%), median DOR of 6.0 months (range: 1.0+ -9.7), and 6-month PFS rate of 40% (95% CI: 24%-55%). Tissue factor expression was confirmed in most patients; no significant association with response was observed., Conclusions: Tisotumab vedotin demonstrated a manageable safety profile and encouraging antitumor activity in patients with previously treated recurrent or metastatic cervical cancer., (©2019 American Association for Cancer Research.)- Published
- 2020
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40. Everolimus, Letrozole, and Metformin in Women with Advanced or Recurrent Endometrioid Endometrial Cancer: A Multi-Center, Single Arm, Phase II Study.
- Author
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Soliman PT, Westin SN, Iglesias DA, Fellman BM, Yuan Y, Zhang Q, Yates MS, Broaddus RR, Slomovitz BM, Lu KH, and Coleman RL
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Everolimus, Female, Humans, Letrozole, Middle Aged, Progression-Free Survival, Carcinoma, Endometrioid, Metformin
- Abstract
Purpose: Treatment for patients with recurrent endometrioid endometrial cancer (EEC) are limited as paclitaxel is the only second-line chemotherapy with a response rate >13%. Targeting PIK3/mTOR in combination with hormonal therapy has shown promise. The addition of metformin may enhance this response. We conducted a phase II study evaluating everolimus, letrozole, and metformin in advanced/recurrent EEC., Patients and Methods: A Simon two-stage design was employed. Women with ≤2 prior chemotherapy regimens for recurrence were eligible. Pretreatment biopsy was required, followed by everolimus 10 mg orally, letrozole 2.5 mg orally, and metformin 500 mg orally twice a day on a 4-week cycle. The primary endpoint was clinical benefit (CB), defined as complete response (CR), partial response (PR), or stable disease (SD) confirmed at 16 weeks. Patients were treated until progression or toxicity., Results: Sixty-two patients were enrolled. Median age was 62 years (40-77) with 401 cycles completed, median of 6 cycles (1-31). Fifty-four patients were evaluable for response with a CB rate of 50% (27/54). Best overall response (OR) was PR 28% (15/54) and SD 22% (12/54). Thirteen patients received >12 cycles. Median follow-up was 17.9 months (2-47). Median progression-free survival was 5.7 [95% confidence interval (CI), 3.0-8.1] and OS was 19.6 months (95% CI, 14.2-26.3). Positive progesterone receptor expression was associated with CB (89.5% vs. 27.3%, P = 0.001)., Conclusions: Everolimus, letrozole, and metformin resulted in 50% CB and 28% OR in women with recurrent EEC. Progesterone receptor-positive tumors may have better response; validation studies are needed. See related commentary by Madariaga et al., p. 523 ., (©2019 American Association for Cancer Research.)
- Published
- 2020
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41. Clear cell carcinoma arising from abdominal wall endometrioma after cesarean section.
- Author
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Lopes A, Anton C, Slomovitz BM, Accardo de Mattos L, and Marino Carvalho F
- Subjects
- Abdominal Neoplasms diagnostic imaging, Abdominal Neoplasms pathology, Abdominal Wall diagnostic imaging, Abdominal Wall pathology, Adenocarcinoma, Clear Cell diagnostic imaging, Adenocarcinoma, Clear Cell pathology, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Cesarean Section, Endometriosis drug therapy, Endometriosis pathology, Female, Humans, Medroxyprogesterone administration & dosage, Middle Aged, Abdominal Neoplasms etiology, Adenocarcinoma, Clear Cell etiology, Endometriosis complications
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2019
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42. Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1-2 trial.
- Author
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de Bono JS, Concin N, Hong DS, Thistlethwaite FC, Machiels JP, Arkenau HT, Plummer R, Jones RH, Nielsen D, Windfeld K, Ghatta S, Slomovitz BM, Spicer JF, Yachnin J, Ang JE, Mau-Sørensen PM, Forster MD, Collins D, Dean E, Rangwala RA, and Lassen U
- Subjects
- Adolescent, Adult, Aged, Angiogenesis Inhibitors administration & dosage, Angiogenesis Inhibitors adverse effects, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Drug-Related Side Effects and Adverse Reactions pathology, Female, Humans, Immunoconjugates adverse effects, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Neoplasms classification, Neoplasms pathology, Oligopeptides adverse effects, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal, Humanized administration & dosage, Drug-Related Side Effects and Adverse Reactions classification, Immunoconjugates administration & dosage, Neoplasms drug therapy, Oligopeptides administration & dosage
- Abstract
Background: Tisotumab vedotin is a first-in-human antibody-drug conjugate directed against tissue factor, which is expressed across multiple solid tumour types and is associated with poor clinical outcomes. We aimed to establish the safety, tolerability, pharmacokinetic profile, and antitumour activity of tisotumab vedotin in a mixed population of patients with locally advanced or metastatic (or both) solid tumours known to express tissue factor., Methods: InnovaTV 201 is a phase 1-2, open-label, dose-escalation and dose-expansion study done at 21 centres in the USA and Europe. Patients (aged ≥18 years) had relapsed, advanced, or metastatic cancer of the ovary, cervix, endometrium, bladder, prostate, oesophagus, squamous cell carcinoma of the head and neck or non-small-cell lung cancer; an Eastern Cooperative Oncology Group performance status of 0-1; and had relapsed after or were not eligible to receive the available standard of care. No specific tissue factor expression level was required for inclusion. In the dose-escalation phase, patients were treated with tisotumab vedotin between 0·3 and 2·2 mg/kg intravenously once every 3 weeks in a traditional 3 + 3 design. In the dose-expansion phase, patients were treated at the recommended phase 2 dose. The primary endpoint was the incidence of adverse events, including serious adverse events, infusion-related, treatment-related and those of grade 3 or worse, and study drug-related adverse events, analysed in all patients who received at least one dose of tisotumab vedotin (full analysis population). This trial is registered with ClinicalTrials.gov, number NCT02001623, and is closed to new participants with follow-up ongoing., Findings: Between Dec 9, 2013, and May 18, 2015, 27 eligible patients were enrolled to the dose-escalation phase. Dose-limiting toxicities, including grade 3 type 2 diabetes mellitus, mucositis, and neutropenic fever, were seen at the 2·2 mg/kg dose; therefore, 2·0 mg/kg of tisotumab vedotin intravenously once every 3 weeks was established as the recommended phase 2 dose. Between Oct 8, 2015, and April 26, 2018, 147 eligible patients were enrolled to the dose-expansion phase. The most common (in ≥20% of patients) treatment-emergent adverse events of any grade were epistaxis (102 [69%] of 147 patients), fatigue (82 [56%]), nausea (77 [52%]), alopecia (64 [44%]), conjunctivitis (63 [43%]), decreased appetite (53 [36%]), constipation (52 [35%]), diarrhoea (44 [30%]), vomiting (42 [29%]), peripheral neuropathy (33 [22%]), dry eye (32 [22%]), and abdominal pain (30 [20%]). The most common adverse events of grade 3 or worse were fatigue (14 [10%] of 147 patients), anaemia (eight [5%]), abdominal pain (six [4%]), hypokalaemia (six [4%]), conjunctivitis (five [3%]), hyponatraemia (five [3%]), and vomiting (five [3%]). 67 (46%) of 147 patients had a treatment-emergent serious adverse event. 39 (27%) of 147 patients had a treatment-emergent serious adverse event related to the study drug. Infusion-related reactions occurred in 17 (12%) of 147 patients. Across tumour types, the confirmed proportion of patients who achieved an objective response was 15·6% (95% CI 10·2-22·5; 23 of 147 patients). There were nine deaths across all study phases (three in the dose-escalation phase and six in the dose-expansion phase); only one case of pneumonia in the dose-expansion phase was considered possibly related to study treatment., Interpretations: Tisotumab vedotin has a manageable safety profile with encouraging preliminary antitumour activity across multiple tumour types in heavily pretreated patients. Continued evaluation of tisotumab vedotin is warranted in solid tumours., Funding: Genmab A/S., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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43. A randomized phase II study of letrozole vs. observation in patients with newly diagnosed uterine leiomyosarcoma (uLMS).
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Slomovitz BM, Taub MC, Huang M, Levenback C, and Coleman RL
- Abstract
Objective: Up to 87% of uterine leiomyosarcomas have estrogen receptor positivity. There are no effective adjuvant therapies for LMS. The objective of this study was to determine the efficacy of letrozole in patients with newly diagnosed uterine leiomyosarcoma (uLMS). The primary endpoint of this study was a reduction in the recurrence rate for patients with this disease., Methods: We performed a randomized, open-label, phase II study of letrozole (experimental arm) administered orally on a daily basis vs. observation (control) in patients with newly diagnosed early stage uLMS. Patient enrollment was to be open to any individual with newly diagnosed uLMS seen in the Gynecologic Oncology Center at M. D. Anderson Cancer Center. Hormone receptor positivity using CLIA approved lab testing was an eligibility requirement. No prior therapy was allowed., Results: Nine patients were randomized. Four patients were in the experimental arm and five patients were in the observation arm. No patients had prior therapy. The median duration of protocol treatment was 43.9 months (range, 6.5-70.2). The median PFS for the experimental arm was not reached (NR) compared to 17.3 months. The percent progression free at 12 and 24 months was 100% for patients receiving letrozole compared to 80% at 12 months and 40% at 24 months for patients in the observation arm., Conclusions: While no definitive conclusions can be made due to early study closure, these early observations warrant further investigation. We desperately need an effective adjuvant therapy for women with early stage uLMS.
- Published
- 2018
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44. Complete Serologic Response to Pembrolizumab in a Woman With Chemoresistant Metastatic Choriocarcinoma.
- Author
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Huang M, Pinto A, Castillo RP, and Slomovitz BM
- Subjects
- Adult, B7-H1 Antigen antagonists & inhibitors, B7-H1 Antigen immunology, Choriocarcinoma blood, Choriocarcinoma immunology, Choriocarcinoma secondary, Female, Humans, Pregnancy, Treatment Outcome, Uterine Neoplasms blood, Uterine Neoplasms immunology, Uterine Neoplasms pathology, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Choriocarcinoma drug therapy, Chorionic Gonadotropin, beta Subunit, Human blood, Drug Resistance, Neoplasm, Uterine Neoplasms drug therapy
- Published
- 2017
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45. Ovarian Cancer: The Fallopian Tube as the Site of Origin and Opportunities for Prevention.
- Author
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George SH, Garcia R, and Slomovitz BM
- Abstract
High-grade serous carcinoma (HGSC) is the most common and aggressive histotype of epithelial ovarian cancer (EOC), and it is the predominant histotype associated with hereditary breast and ovarian cancer syndrome (HBOC). Mutations in BRCA1 and BRCA2 are responsible for most of the known causes of HBOC, while mutations in mismatch repair genes and several genes of moderate penetrance are responsible for the remaining known hereditary risk. Women with a history of familial ovarian cancer or with known germline mutations in highly penetrant genes are offered the option of risk-reducing surgery that involves the removal of the ovaries and fallopian tubes (salpingo-oophorectomy). Growing evidence now supports the fallopian tube epithelia as an etiological site for the development of HGSC and consequently, salpingectomy alone is emerging as a prophylactic option. This review discusses the site of origin of EOC, the rationale for risk-reducing salpingectomy in the high-risk population, and opportunities for salpingectomy in the low-risk population.
- Published
- 2016
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46. Reply to G. Bogani et al.
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Slomovitz BM and Coleman RL
- Subjects
- Female, Humans, Endometrial Neoplasms drug therapy, Nitriles administration & dosage, Sirolimus analogs & derivatives, Triazoles administration & dosage
- Published
- 2015
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47. Update on sentinel lymph node biopsy for early-stage vulvar cancer.
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Slomovitz BM, Coleman RL, Oonk MH, van der Zee A, and Levenback C
- Subjects
- Female, Humans, Lymphatic Metastasis, Neoplasm Staging, Lymph Nodes pathology, Sentinel Lymph Node Biopsy methods, Vulvar Neoplasms pathology
- Abstract
Two prospective, multicenter clinical trials have demonstrated the feasibility and reproducibility of sentinel lymph node (SLN) biopsy as part of the standard management of early-stage vulvar carcinoma. On the basis of the results of these trials, many gynecologic oncologists have incorporated SLN biopsy for vulvar cancer into their practice. Studies have further shown that SLN biopsy is associated with better quality of life than full lymphadenectomy, is more cost-effective than full lymphadenectomy, and improved pathologic evaluation. A large observational study is currently evaluating the outcomes of patients with early-stage vulvar cancer according to the results of their SLN biopsy and the approach to their care; this study may confirm that full inguinofemoral lymphadenectomy is no longer necessary in most patients with this disease. Here, we review the published data supporting SLN biopsy as part of the standard of care for women with early-stage vulvar cancer and discuss future considerations for the management of this disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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48. Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma.
- Author
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Slomovitz BM, Jiang Y, Yates MS, Soliman PT, Johnston T, Nowakowski M, Levenback C, Zhang Q, Ring K, Munsell MF, Gershenson DM, Lu KH, and Coleman RL
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Bayes Theorem, Biomarkers, Tumor, Cohort Studies, DNA Mutational Analysis, Disease-Free Survival, Endometriosis complications, Everolimus, Female, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Immunosuppressive Agents administration & dosage, Letrozole, Middle Aged, Neoplasm Recurrence, Local, Phosphoinositide-3 Kinase Inhibitors, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism, Sirolimus administration & dosage, TOR Serine-Threonine Kinases metabolism, Time Factors, Treatment Outcome, beta Catenin genetics, Endometrial Neoplasms drug therapy, Nitriles administration & dosage, Sirolimus analogs & derivatives, Triazoles administration & dosage
- Abstract
Purpose: The phosphoinositol-3 kinase (PI3K) pathway is frequently dysregulated in endometrial cancer (EC). Hormonal manipulation leads to response in some patients with EC, but resistance derived from PI3K pathway activation has been documented. Targeting mammalian target of rapamycin (mTOR) may overcome endocrine resistance. We conducted a two-institution phase II trial of everolimus and letrozole in women with recurrent EC., Patients and Methods: Patients were considered incurable, had measurable disease, and were treated with up to two prior cytotoxic regimens. Everolimus was administered orally at 10 mg daily and letrozole was administered orally at 2.5 mg daily. Each cycle consisted of 4 weeks of therapy. Patients were treated until progression, toxicity, or complete response (CR). The primary end point was the clinical benefit rate (CBR), which was defined as CR, partial response, or stable disease (≥ 16 weeks) by RECIST 1.0 criteria. Translational studies were performed to correlate biomarkers with response., Results: Thirty-eight patients were enrolled (median age, 62 years; range, 24 to 82 years). Thirty-five patients were evaluable for response. The CBR was 40% (14 of 35 patients); the median number of cycles among responders was 15 (range, seven to 29 cycles). The confirmed objective response rate (RR) was 32% (11 of 35 patients; nine CRs and two partial responses; median, 15 cycles; range, eight to 29 cycles). Twenty percent of patients (seven of 35 patients) were taken off treatment after a prolonged CR and at the discretion of the treating clinician. None of the patients discontinued treatment as a result of toxicity. Serous histology was the best predictor of lack of response. Patients with endometrioid histology and CTNNB1 mutations responded well to everolimus and letrozole., Conclusion: Everolimus plus letrozole results in a high CBR and RR in patients with recurrent EC. Further development of this combination in recurrent endometrioid EC is under way., (© 2015 by American Society of Clinical Oncology.)
- Published
- 2015
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49. Incidental power morcellation of malignancy: a retrospective cohort study.
- Author
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Graebe K, Garcia-Soto A, Aziz M, Valarezo V, Heller PB, Tchabo N, Tobias DH, Salamon C, Ramieri J, Dise C, and Slomovitz BM
- Subjects
- Cohort Studies, Female, Humans, Hysterectomy methods, Leiomyoma surgery, Middle Aged, Retrospective Studies, Uterine Myomectomy methods, Uterine Neoplasms surgery, Leiomyoma pathology, Uterine Neoplasms pathology
- Abstract
Objective: Uterine fibroids often require hysterectomy via a laparotomy or utilizing minimally invasive surgical (MIS) approach. Morcellation is a fragmentation of the uterus into smaller pieces. The objective of this study is to determine the incidence of malignancies found in morcellated specimens at our institution., Methods: Women who had a minimally invasive hysterectomy, for presumptive benign uterine conditions were identified, included and reviewed. Patients were divided into two groups being either benign disease or malignancies. The continuous variables uterine weight and patient age were tested for normalcy with the Shapiro-Wilk test. The exposure of subspecialist vs general gynecology was interrogated via a Chi-Squared analysis., Results: 10 cases of malignancies were identified including endometrioid endometrial carcinomas (3), uterine serous carcinoma (1), endometrial stromal sarcomas (ESS) (3), and leiomyosarcomas (LMS) (3). An overall risk of occult cancer on a morcellated specimen was .73%; leiomyosarcoma was 0.22%, endometrial stromal sarcoma 0.22%, and endometrial cancer 0.29%. The median uterine weight for the 10 morcellated malignancies was 293.5g whereas the median weight for the benign uteri was only 117.5g giving a theta of -106 (95% CI -261,20). There was no difference in patient age or surgeon type between the groups (See Table 1)., Conclusions: Morcellation was associated with substantially higher risk of abdominopelvic recurrence and lower disease-free survival. Morcellated uterine malignancies were significantly heavier than benign uteri. Further research on uterine morcellation should focus on decision and cost-benefit analyses to determine the ideal candidate in whom uterine morcellation during minimally invasive hysterectomy would facilitate more good than harm., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2015
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50. Accuracy of robotic sentinel lymph node detection (RSLND) for patients with endometrial cancer (EC).
- Author
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Desai PH, Hughes P, Tobias DH, Tchabo N, Heller PB, Dise C, and Slomovitz BM
- Subjects
- Adenocarcinoma pathology, Adenocarcinoma secondary, Adenocarcinoma surgery, Adenocarcinoma, Clear Cell pathology, Adenocarcinoma, Clear Cell secondary, Adult, Aged, Aged, 80 and over, Carcinoma, Endometrioid pathology, Carcinoma, Endometrioid secondary, Carcinosarcoma pathology, Carcinosarcoma secondary, Coloring Agents, Endometrial Neoplasms pathology, Female, Humans, Hysterectomy, Methylene Blue, Middle Aged, Ovariectomy, Pelvis, Retrospective Studies, Salpingectomy, Adenocarcinoma, Clear Cell surgery, Carcinoma, Endometrioid surgery, Carcinosarcoma surgery, Endometrial Neoplasms surgery, Lymph Nodes pathology, Robotic Surgical Procedures methods, Sentinel Lymph Node Biopsy methods
- Abstract
Objectives: Lymphadenectomy as a part of the staging for EC patients is controversial. Sentinel lymph node detection has been introduced to determine which patients would benefit from adjuvant therapy and to limit morbidities associated with a full pelvic nodal dissection. The purpose of this study is to evaluate diagnostic accuracy and detection rate of robotic sentinel lymph node detection (RSLND) as a part of the surgical staging for EC., Methods: A retrospective database of all patients who underwent intraoperative lymphatic mapping using cervical injection methylene blue followed by RSLND as a part of their procedure was reviewed. Sentinel lymph node (SLN) was initially examined by routine Hematoxylin and Eosin (H&E) and ultrastaging by immunohistochemistry (IHC)., Results: Between 4/2011 and 6/2013, 120 patients with endometrial cancer underwent RSLND. The median age was 62years (25-87); median BMI was 32 (18-76). Out of 120 patients, only one patient underwent RSLND with fertility preservation; and 119 patients underwent robotic hysterectomy and surgical staging with RSLND. None of the cases was converted to an open procedure. At least 1 SLN was detected in 86% (103/120) of the patients. Bilateral SLNs were detected in 52% (62/120). Positive nodes were identified in 8% (10/120) of the patients. Of those with SLN (+), 50% (5/10) were by ultrastaging (IHC) alone. No patients had positive regional nodes without SLN (+)., Conclusions: RSLND using methylene blue cervical injection can identify SLN in most patients with EC. IHC ultrastaging improves the detection of node positive disease when compared to traditional pathological evaluation., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
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