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Objectives: Real-world data evaluating how approvals of novel treatment regimens for ovarian cancer have impacted the treatment paradigm, including first-line maintenance, are lacking. This analysis aimed to describe treatment patterns for advanced epithelial ovarian cancer in Europe and the USA in the first-line maintenance setting. Patient characteristics, biomarker testing rates, and drivers of treatment choice were also evaluated., Methods: A retrospective chart review study of electronic medical records in Europe and the USA was conducted for patients diagnosed with epithelial ovarian cancer (June 1, 2017-May 31, 2020), in line with Healthcare Market Research guidelines. Eligible physicians extracted data from electronic medical records by completing standardized patient record forms, including questions on patient involvement in treatment decisions. Patients with advanced (stage III/IV) disease were stratified by country and diagnosis date to provide information on treatment patterns., Results: Patient record forms for 7072 patients with epithelial ovarian cancer were completed by 416 physicians; 5386 patients had stage III/IV ovarian cancer. Over time, the percentage of patients who were tested for BRCA mutations or homologous recombination deficiency increased. Patient preference was documented as a reason for treatment selection in approximately one-sixth of cases in the first-line adjuvant and first-line maintenance settings. The use of first-line maintenance poly(ADP-ribose) polymerase inhibitor monotherapy increased over time, while the use of vascular endothelial growth factor inhibitor monotherapy decreased., Conclusions: This real-world study showed that treatment patterns for advanced epithelial ovarian cancer varied by country. Rates of physician-reported patient involvement in treatment decisions in the first-line adjuvant and maintenance treatment settings for ovarian cancer were low, highlighting an unmet need for initiatives to improve patient involvement in shared decision-making regarding maintenance therapy selection., Competing Interests: Competing interests: The authors disclose the following potential conflicts of interest: KNM: Institutional research grant: Angle PLC; Consulting fees: Fujirebio Diagnostics Inc; Advisory fees: GSK. MRM: Advisory board fees: Allarity Therapeutics, AstraZeneca, Biocad, BioNTech, Boehringer Ingelheim, Clovis, Daiichi-Sankyo, Eisai, Genmab, GSK, ImmunoGen, Incyte, Karyopharm, Merck/MSD, Mersana, Novartis, Regeneron, Roche, Seagen, Takeda, Tesaro, Zailab; membership on the board of directors or stockholder/shareholder: Karyopharm Therapeutics, Sera Prognostics; Institutional research grants: Allarity, Apexigen, AstraZeneca, Boehringer Ingelheim, Clovis, GSK, Novartis, Tesaro, Ultimovacs; Trial chair: AstraZeneca, Boehringer Ingelheim, Deciphera, Daiichi-Sankyo, GSK, Merck, Mersana, NuvationBio, Tesaro. SP: Honoraria: AstraZeneca, GSK, MSD, Roche; Research funding: AstraZeneca, GSK, MSD, Pfizer, Roche. CG: Honoraria/consultancy fees: AstraZeneca, Chugai, Clovis, Cor2Ed, Eisai, GSK, MSD, Peer Voice, Takeda; Research funding: Aprea, Artios, AstraZeneca, BerGen Bio, GSK, Medannexin, MSD, Novartis, NuCana; Issued/pending patents related to predicting treatment response in ovarian cancer. DL: Grants or contracts: Alkermes, AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, ImmunoGen, Incyte, MSD, Novartis, Pharma&, Pharmamar, Roche, Seagen; Consulting fees: AstraZeneca, Clovis Oncology, Corcept, Daiichi Sankyo, Genmab, GSK, ImmunoGen, MSD, Novartis, Novocure, Oncoinvest, Seagen, Sutro; Honoraria: AstraZeneca, Corcept, Genmab, GSK, ImmunoGen, MSD, Seagen; Support for attending meetings and/or travel: AstraZeneca, GSK, Menarini, MSD; Participation on a data safety monitoring board or advisory board: AstraZeneca, Clovis Oncology, Corcept, Daiichi Sankyo, Genmab, GSK, ImmunoGen, MSD, Novocure, Oncoinvest, Seagen, Sutro; Leadership or fiduciary roles: ENGOT, GCIG, MITO. BJM: Consulting fees: Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Eisai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Iovance, Karyopharm, Laekna, MacroGenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, Teasro/GSK, US Oncology Research, VBL, Verastem, Zentalis; Speakers’ bureau honoraria: AstraZeneca, Eisai, Myriad, Roche/Genentech, Tesaro/GSK. JS: Grants or contracts: GSK, Roche; Consulting fees: Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Merck Sharp & Dohme, MSD, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche; Honoraria fees: AstraZeneca, Clovis, Eisai, MSD, PharmaMar, Roche, Tesaro/GSK; Support for attending meetings: AstraZeneca, PharmaMar, Roche, Tesaro/GSK. JMS: Employee of GSK. ND'E: Employee of Genactis (the company that was contracted to perform the statistical analyses). AG-M: Fees for different educational or advisory-related activities: Alkermes, Amgen, AstraZeneca, Clovis, Eisai, Genmab, GSK, Hedera Dx, Immunogen, Illumina, Karyopharm, Macrogenics, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Regeneron, Roche, Seagen, Sotio, Sutro, Takeda, Tubulis., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Competing Interests: Competing interests: BJM reports personal fees from Agenus, Acrivon, Adaptimune, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Easai, 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, outside the submitted work. RLC reports personal fees from Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, OncoQuest, Onxerna, Regeneron, Roche/Genentech, Novocure, Merck, Abbvie outside the submitted work. MRM reports personal fees from AstraZeneca, Clovis, personal fees from GSK outside the submitted work.

Background: Optimal treatment of cervical cancer is based on disease stage; therefore, an understanding of the global epidemiology of specific stages of locally advanced disease is needed., Objective: This systematic literature review was conducted to understand the global and region-specific proportions of patients with cervical cancer with locally advanced disease and to determine the incidence of the locally advanced disease., Methods: Systematic searches identified observational studies published in English between 2010 and June 10, 2020, reporting the proportion of patients with, and/or incidence of, locally advanced stages of cervical cancer (considered International Federation of Gynecology and Obstetrics (FIGO) IB2-IVA). Any staging criteria were considered as long as the proportion with locally advanced disease was distinguishable. For each study, the proportion of locally advanced disease among the cervical cancer population was estimated., Results: The 40 included studies represented 28 countries in North or South America, Asia, Europe, and Africa. Thirty-eight studies reported the proportion of locally advanced disease among populations with cervical cancer. The estimated median proportion of locally advanced disease among all cervical cancer was 37.0% (range 5.6-97.5%; IQR 25.8-52.1%); estimates were generally lowest in North America and highest in Asia. Estimated proportions of ≥50% were reported in nine studies from Asia, Europe, Brazil, and Morocco; estimates ≤25% were reported in six studies from Asia, United States, Brazil, and South Africa. Locally advanced disease was reported for 44% and 49% of women aged >70 and ≥60 years, and 5-100% of younger women with cervical cancer. A greater proportion of locally advanced disease was reported for Asian American (19%) versus White women (8%) in one United States study. Two of five studies describing the incidence of locally advanced disease reported rates of 2-4/100 000 women among different time frames., Conclusion: This review highlights global differences in proportions of locally advanced cervical cancer, including regional variance and disparities according to patient race and age., Competing Interests: Competing interests: BJM reports personal fees from Abbvie, Advaxis, Agenus, Amgen, AstraZeneca, Biodesix, Clovis, Conjupro, Genmab, Gradalis, ImmunoGen, Immunomedics, Incyte, Janssen/Johnson & Johnson, Mateon (formally Oxigene), Merck, Myriad, Perthera, Pfizer, Precision Oncology, Puma, Roche/Genentech, Samumed, Takeda, TESARO, Inc., and VBL, outside the submitted work. DT is supported by grants from the Singapore Ministry of Health’s National Medical Research Council and Pangestu Family Foundation Gynaecological Cancer Research Fund. He also reports personal fees from AstraZeneca, Roche, MSD, Merck Serono, GSK, Tessa Therapeutics, Eisai, and Genmab; research funding and support from AstraZeneca, Roche, Bayer, BMS, MSD, Eisai, and Karyopharm; stock ownership in the Asian Microbiome Library (AMiLi). All of these have been received outside the submitted work. JT has nothing to disclose. ATN, JDHC, and MP are employees and shareholders of AstraZeneca. EP-L reports personal fees and non-financial support from AstraZeneca, Tesaro/GSK, Roche; personal fees from Clovis, Incyte, and Pfizer; and other from ARCAGY-Research, outside the submitted work., (© IGCS and ESGO 2022. Re-use permitted under CC BY. Published by BMJ.)

Cervical cancer constitutes a significant health burden for women globally. While most patients with early-stage disease can be cured with radical surgery or chemoradiotherapy, patients with high-risk locally advanced disease or with recurrent/metastatic disease have a poor prognosis with standard treatments. Immunotherapies are a rational treatment for this HPV-driven cancer that commonly expresses programmed cell death ligand-1. Before 2021, pembrolizumab was the only United States Food and Drug Administration-approved immunotherapy in cervical cancer, specifically for the second-line recurrent or metastatic (r/m) setting. In late 2021, the antibody-drug conjugate tisotumab vedotin was approved for second-line r/m cervical cancer and pembrolizumab combined with chemotherapy ± bevacizumab was approved for first-line r/m disease based on results from KEYNOTE-826. Moreover, with at least 2 dozen additional immunotherapy clinical trials in the second-line and first-line r/m setting, as well as in locally advanced disease, the treatment landscape for cervical cancer may eventually encounter a potential paradigm shift. Pivotal trials of immunotherapies for cervical cancer that were recently approved or with the potential for regulatory consideration through 2024 are reviewed. As immunotherapy has the opportunity to establish new standards of care in the treatment of cervical cancers, new biomarkers to identify the ideal patient populations for these therapies may also become important. However, issues with access, affordability, and compliance in low- and middle-income countries are anticipated., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To characterize clinical outcomes of women with advanced/recurrent endometrial cancer (AEC) in routine practice using electronic health records from a real-world database., Methods: Adult women diagnosed with AEC (stage III/IV, or early stage with locoregional/distant recurrence) between January 1, 2013 and September 30, 2020, inclusive, were eligible provided they received platinum-based chemotherapy at any time following diagnosis and had ≥2 clinical visits. Follow-up was from initiation of systemic treatment after advanced diagnosis (index) until March 30, 2021, last available follow-up, or death, whichever occurred first. Outcomes, by histological subtype, included Kaplan-Meier estimates of overall survival (OS) and time to first subsequent therapy or death (TFST)., Results: Of the 2202 women with AEC, most were treated in a community setting (82.7%) and presented with stage III/IV disease at initial diagnosis (74.0%). The proportion with endometrioid carcinoma, uterine serous carcinoma (USC), and other AEC subtypes was 59.8%, 25.0%, and 15.2%, respectively. The most common first systemic treatment following advanced/recurrent diagnosis was platinum-based combination chemotherapy (82.0%). Median OS (95% CI) from initiation of first systemic treatment was shorter with USC (31.3 [27.7-34.3] months) and other AECs (29.4 [21.4-43.9] months) versus endometrioid carcinoma (70.8 [60.5-83.2] months). Similar results were observed for TFST. Black/African American women had worse OS and TFST than white women., Conclusions: Women with AEC had poor survival outcomes, demonstrating the requirement for more effective therapies. To our knowledge, this is the most comprehensive evaluation of contemporary treatment of AEC delivered in a community setting to date., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the presentation, characteristics, and prognostic significance of symptoms in patients with high-risk early-stage epithelial ovarian cancer., Methods: A retrospective chart review was performed on all patients enrolled in a phase III clinical trial (GOG 157). All patients had surgically staged, high-risk early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II). Chi-square and Kaplan-Meier estimates and Cox proportional hazards models were used for statistical analyses., Results: Of 419 patients evaluated for symptoms, 301 (72%) presented with one or more symptoms, and 118 (28%) were asymptomatic but had a mass found on examination. Forty percent had only one symptom, and 32% had more than one symptom. Among those with at least one symptom, the most common were abdominal and pelvic pain (31%), and increased girth or fullness (26%). Overall, 23% of patients with tumors 10 cm or smaller, 27% of patients with tumors larger than 10 cm to 15 cm, and 46% of patients with tumors larger than 15 cm had multiple symptoms (P<.001). There was no significant difference in presentation of symptoms based on age, stage, or histologic subtype. Symptoms at diagnosis were not associated with recurrence or survival., Conclusion: More than 70% of patients with high-risk early-stage, epithelial ovarian cancer present with one or more symptoms, with the most common being abdominal or pelvic pain. The proportion of women with symptoms and the number of symptoms increase with enlarging tumor size., Competing Interests: Financial Disclosure Dr. John K. Chan received funds from NRG/GOG for consortium trial participation and funds for research, consultant, and speaker bureau from AbbVie, Acerta, Aravive, AstraZeneca, Clovis, Eisai, GlaxoSmithKline, Merck, Myriad, Roche, Seagen. Bradley J. Monk is on the board for the GOG Foundation and is a paid consultant. Brittany Davidson received money from GSK. Joan L. Walker disclosed that Stephenson Cancer Center is an NRG Oncology Laps site and she is NCORP PI, but unrelated to this study. Robert Wenham received GOG funds for consortium trial participation, money from Regeneron, Tesaro/GSK, and Genentech. In the past 3 years, he has received funds from Seagen, Ovation Diagnostics, AbbVie, Clovis, AstraZeneca, Prescient Therapeutics, and Merck. Yovanni Casablanca received funding from AstraZeneca. Nick M. Spirtos received funding from John Wiley and Sons, and NRG Oncology. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Recently, Vigil showed significant clinical benefit with improvement in relapse free (RFS) and overall survival (OS) in pre-planned subgroup analysis in stage III/IV newly diagnosed ovarian cancer patients with BRCA wild type (BRCA-wt) molecular profile. Here we analyze homologous recombination (HR) status of patients enrolled in the Phase 2b VITAL study and determine clinical benefit of Vigil in HR proficient (P) patients., Methods: Patients were previously enrolled in a Phase 2b, double-blind, placebo-controlled trial. All were in complete response with Stage III/IV high grade serious, endometroid or clear cell ovarian cancer. HR status was determined using MyChoice®CDx score (<42 = HRP) (Myriad Genetics, Inc., UT). Post-hoc analyses were carried out using Kaplan Meier and restricted mean survival time (RMST) analysis to evaluate RFS and OS based on HR deficiency (D) status., Results: RFS was improved with Vigil (n = 25) in HRP patients compared to placebo (n = 20) (HR = 0.386; 90% CI 0.199-0.750; p = 0.007), results were verified by RMST (p = 0.017). Similarly, OS benefit was observed in Vigil group compared to placebo (HR = 0.342; 90% CI 0.141-0.832; p = 0.019). Results with OS were also verified with RMST (p = 0.008)., Conclusion: Vigil exhibited clinical benefit in HRP molecular profile patients., Competing Interests: Declaration of Competing Interest RPR reports sponsored research related to this work. BJM reports personal fees from Abbvie, Advaxis, Agenus, Amgen, Aravive, AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoCare, ChemoID, Circulogene, Clovis, Conjupro, Easai, Geistlich, Genmab/Seattle Genetics, GOG Foundation, Gradalis, ImmunoGen, Immunomedics, Incyte, Janssen/ Johnson & Johnson, Laekna Health Care, Mateon (formally Oxigene), Merck, Mersana, Myriad, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Precision Oncology, Puma, Regeneron, Roche/ Genentech, Samumed, Takeda, Tesaro/GSK, VBL, and Vigeo, outside the submitted work. EG reports personal fees or grant funding from MedImmune, Gradalis, Agios Pharmaceuticals, Karyopharm, Tracon, Genentech, Bristol Myers Squibb, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021. Published by Elsevier Inc.)

Objective: There is no standard systemic treatment for recurrent or metastatic cervical cancer (r/mCC) after failure of first-line (1L) therapy. This study characterizes the patient experience, treatment patterns, and clinical outcomes of patients who initiated second-line (2L) therapy for r/mCC in a US community oncology setting., Methods: This is an observational study of cervical cancer patients who failed 1L systemic treatment for r/mCC and initiated 2L systemic therapy between 2014 and 2019 within the US Oncology Network (USON). USON's electronic health records were used to identify eligible patients and abstract data. Overall survival (OS), time to treatment discontinuation (TTD), and time to first subsequent treatment (TFST) were estimated using Kaplan-Meier methods., Results: A total of 130 patients were identified (mean age 53 years). Over 60% of patients had Eastern Cooperative Oncology Group score of 0-1. Cytotoxic monotherapy was the most frequently prescribed regimen (N = 60, 46%) in 2L, followed by combination therapies (N = 45, 35%), pembrolizumab monotherapy (N = 19, 15%), and bevacizumab monotherapy (N = 6, 5%). Median OS was 9.1 months (95% CI: 7.2-12.2) after initiation of 2L therapy. Median TTD was 2.8 months (95% CI: 2.5-3.3), and median TFST was 4.9 months (95% CI: 4.2-5.7). No significant difference in outcomes was found when stratified by 2L treatments., Conclusions: The observed heterogeneity in 2L r/mCC therapy suggests no clear standard-of-care in this setting. Additionally, short duration of OS observed was consistent across 2L regimens. New, effective treatment options in this setting are needed., Competing Interests: Declaration of Competing Interest Bradley J. Monk has received honorarium/consultant fees from Agenus, Akeso Bio, Aravive, Elevar Therapeutics, Genmab/Seagen Inc., GOG Foundation, Gradalis, ImmunoGen, Karyopharm, Iovance, McKesson/US Oncology, Mersana, Novocure, Myriad, Pfizer, Puma, VBL, and honorarium/consulting/speaking fees from AstraZeneca, Clovis, Easai, Merck, Roche/Genentech, and Tesaro/GSK. Jie Ting is an employee of Seagen Inc. and owns stock in Seagen Inc. Sonia Pulgar is an employee of Seagen Inc. and owns stock in Seagen Inc. Marley Boyd is an employee of McKesson, which received consulting fees in connection with this study from Seagen, Inc. Lavanya Sudharshan is an employee of McKesson, which received consulting fees in connection with this study from Seagen, Inc., Savreet Bains is an employee of Genmab. Leonardo Nicacio is an employee of Seagen Inc. and owns stock in Seagen Inc. Robert L. Coleman has received research support and consulting fees from AstraZeneca, Clovis, Genmab, Roche/Genentech, Janssen, and Immunogen, research support from Merck, and consulting fees from GSK, Agenus, OncoQuest, and Gradalis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.)

During a career, which spanned nearly 60 years, Professor Philip J. DiSaia (1937-2018) trailblazed a path forward in academic medicine, which would become the standard by which Departments of Obstetrics and Gynecology and Gynecologic Oncology Divisions and Cancer Centers would be measured throughout the United States, in Europe and Japan. Following his discovery of fetal warfarin syndrome as a resident, DiSaia would serve in the U.S. Navy and successfully compete for an American Cancer Society Grant that would fund his Fellowship in Gynecologic Oncology under the instruction of Dr Felix N. Rutledge at the MD Anderson Hospital and Tumor Institute in Houston, Texas. Dr DiSaia's goal to establish a traditional academic department was realized at the University of California, Irvine, where he remained active in an unprecedented, uninterrupted 42-year run, training many outstanding obstetrician-gynecologists and gynecologic oncologists, future Division Directors, Cancer Center Directors and Department Chairpersons. His dedication to the field and inexhaustible work ethic fueled his many successes in tumor immunology and the clinical trials of the National Cancer Institute's Gynecologic Oncology Group., (© 2020 Japan Society of Obstetrics and Gynecology.)

Background: Olaparib was approved on December 19, 2014 by the US FDA as 4th-line therapy (and beyond) for patients with germline BRCA1/2 mutations; rucaparib was approved on December 19, 2016 as 3rd-line therapy (and beyond) for germline or somatic BRCA1/2-mutated recurrent disease. On October 23, 2019, niraparib was approved for treatment of women with damaging mutations in BRCA1/2 or other homologous recombination repair genes who had been treated with three or more prior regimens. We compared the cost-effectiveness of PARPi(s) with intravenous regimens for platinum-resistant disease., Methods: Median progression-free survival (PFS) and toxicity data from regulatory trials were incorporated in a model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2017, each PARPi(s) was compared separately to non‑platinum-based and bevacizumab-containing regimens. Costs of IV drugs, managing toxicities, infusions, and supportive care were estimated using 2017 Medicare data. Incremental cost-effectiveness ratios (ICERs) were calculated and PFS was reported in quality adjusted life months for platinum-resistant populations., Results: Non‑platinum-based intravenous chemotherapy was most cost effective ($6,412/PFS-month) compared with bevacizumab-containing regimens ($12,187/PFS-month), niraparib ($18,970/PFS-month), olaparib ($16,327/PFS-month), and rucaparib ($16,637/PFS-month). ICERs for PARPi(s) were 3-3.5× times greater than intravenous non‑platinum-based regimens., Conclusion: High costs of orally administered PARPi(s) were not mitigated or balanced by costs of infusion and managing toxicities of intravenous regimens typically associated with lower response and shorter median PFS. Balancing modest clinical benefit with costs of novel therapies remains problematic and could widen disparities among those with limited access to care., Competing Interests: Declaration of competing interest JW reports personal fees for serving on an advisory board for Tesaro in the past 36 months, not related to the submitted work. JB and RB have nothing to disclose. KM 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, 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, all outside the submitted work; . BM 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, from Boston Biomedical, personal fees from ChemoCare, personal fees from ChemoID, personal fees from Circulogene, personal fees from Clovis, personal fees from Conjupro, 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, all outside the submitted work. KT reports personal fees and non-financial support from Genentech, personal fees and non-financial support from Merck, personal fees and non-financial support from Clovis, personal fees and non-financial support from Tesaro, non-financial support from Abbie, personal fees and non-financial support from Astra-Zeneca, non-financial support from Morphotek, personal fees and non-financial support from Genmab, all outside the submitted work., (Copyright © 2020. Published by Elsevier Inc.)

Background: Late-line treatment options for patients with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10%, and median overall survival after third-line therapy of 5-9 months. In this study (QUADRA), we investigated the activity of niraparib monotherapy as the fourth or later line of therapy., Methods: QUADRA was a multicentre, open-label, single-arm, phase 2 study that evaluated the safety and activity of niraparib in adult patients (≥18 years) with relapsed, high-grade serous (grade 2 or 3) epithelial ovarian, fallopian tube, or primary peritoneal cancer who had been treated with three or more previous chemotherapy regimens. The study was done in the USA and Canada, and 56 sites screened patients (50 sites treated at least one patient). Patients received oral niraparib 300 mg once daily continuously, beginning on day 1 and every cycle (28 days) thereafter until disease progression. The primary objective was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with homologous recombination deficiency (HRD)-positive tumours (including patients with BRCA and without BRCA mutations) sensitive to their last platinum-based therapy who had received three or four previous anticancer therapy regimens (primary efficacy population). Efficacy analyses were additionally done in all dosed patients with measurable disease at baseline., Findings: Between April 1, 2015 and Nov 1, 2017, we screened 729 patients for eligibility and enrolled 463 patients, who were initiated on niraparib therapy. At the time of database lock (April 11, 2018), enrolment had closed and the study was ongoing, with 21 patients still on treatment. Patients had received a median of four (IQR 3-5) previous lines of therapy, and the median follow-up for overall survival was 12·2 months (IQR 3·7-22·1). 151 (33%) of 463 patients were resistant and 161 (35%) of 463 patients were refractory to the last administered platinum therapy. 13 (28%) of 47 patients in the primary efficacy population achieved an overall response according to RECIST (95% CI 15·6-42·6; one-sided p=0·00053). The most common drug-related grade 3 or worse treatment-emergent adverse events were anaemia (113 [24%] of 463 patients) and thrombocytopenia (95 [21%] of 463 patients). The most common treatment-emergent serious adverse events were small intestinal obstruction (34 [7%] of 463 patients), thrombocytopenia (34 [7%] of 463 patients), and vomiting (27 [6%] of 463 patients). One death due to gastric haemorrhage was considered treatment related., Interpretation: We observed clinically relevant activity of niraparib among women with heavily pretreated ovarian cancer, especially in patients with HRD-positive platinum-sensitive disease, which includes not only patients with a BRCA mutation but also a population with BRCA wild-type disease. We identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations., Funding: Tesaro., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To assess whether there is an association of patient sociodemographic factors with stage at diagnosis, treatment, and overall survival in patients with vulvar cancer in the National Cancer Database., Methods: This was a retrospective cohort study of patients with primary squamous vulvar carcinoma identified from the National Cancer Database (1998-2004). Multivariate logistic regression was conducted to examine risk factors associated with advanced-stage (stage III or IV) disease at diagnosis. Multivariable Cox regression models were performed to explore risk factors associated with 5-year all-cause mortality., Results: Of 11,153 patients, 42.3% (n=4,713) were diagnosed with stage I disease, 24.6% (n=2,745) stage II, 22.9% (n=2,556) stage III, and 10.2% (n=1,139) stage IV. Advanced stage was significantly associated with older age, nonprivate insurance, and treatment at a lower case volume center (P<.01). Of note, roughly 30% of patients with advanced-stage disease did not receive radiation therapy. Within the advanced stages, age 60 years or older and insurance type were associated with decreased survival (P<.01). In stage III disease, only black race and treatment at a community hospital were associated with a lower risk of death (P<.01)., Conclusion: Patient sociodemographic and clinical characteristics are significantly associated with vulvar cancer stage presentation, treatment, and survival. Unfortunately, within this disease, surgical approaches and adjuvant radiation do not appear consistent., Level of Evidence: II.

The FDA approval of the PARP inhibitor olaparib for fourth-line therapy of germline BRCA1/2-mutated ovarian cancer represents the first registered indication for this class of drugs in any disease. PARP is a family of proteins involved in the repair of single-strand DNA breaks. High-grade serous ovarian carcinomas with BRCA deficiencies may be particularly vulnerable to both direct and indirect effects of PARP inhibition. This phenotype frequently arises as a consequence of defects in the repair of damaged DNA, rendering cancer cells susceptible to DNA-damaging platinum compounds and targeted therapies affecting homologous recombination repair (HRR). When cells already deficient in HRR are exposed to PARP inhibitors, apoptosis occurs by way of synthetic lethality. In this review, we trace the clinical development of olaparib for women with recurrent epithelial ovarian carcinoma harboring germline BRCA mutations, a biomarker for HRR deficiency present in 15% to 20% of cases. Clinical trials highlighted include not only those pivotal studies that have led to regulatory approval in the United States and in Europe, but also those in which olaparib was studied in novel combinations, including chemotherapy and antiangiogenesis agents., (©2015 American Association for Cancer Research.)

Background: GOG 240 was a practice-changing randomised phase 3 trial that concluded that chemotherapy plus bevacizumab for advanced cervical cancer significantly improves overall and progression-free survival, and the proportion of patients achieving an overall objective response, compared with chemotherapy alone. In this study, we aimed to analyse patient-reported outcomes in GOG 240., Methods: Eligible adult participants (aged ≥18 years) had primary stage IVB or recurrent or persistent carcinoma of the cervix with measurable disease and GOG performance status of 0-1. Participants were randomly assigned by web-based permuted block randomisation (block size 4) in a 1:1:1:1 ratio to the four treatment groups: cisplatin (50 mg/m(2) intravenously on day 1 or 2 of the treatment cycle) and paclitaxel (135 mg/m(2) intravenously over 24 h or 175 mg/m(2) intravenously over 3 h on day 1), with or without bevacizumab (15 mg/kg intravenously on day 1 or 2), or paclitaxel (175 mg/m(2) over 3 h on day 1) and topotecan (0·75 mg/m(2) for 30 min on days 1-3) with or without bevacizumab (15 mg/kg intravenously on day 1). Treatment assignment was concealed at randomisation (everyone was masked to treatment assignment, achieved by the use of a computer encrypted numbering system at the National Cancer Institute) and became open-label when each patient was registered to the trial. Treatment cycles were repeated every 21 days until disease progression or unacceptable toxicity, whichever occurred first. The coprimary endpoints of the trial were overall survival and safety; the primary quality-of-life endpoint was the score on the Functional Assessment of Cancer Therapy-Cervix Trial Outcome Index (FACT-Cx TOI). For our analysis of patient-reported outcomes, participants were assessed before treatment cycles 1, 2, and 5, and at 6 and 9 months after the start of cycle 1, with the FACT-Cx TOI, items from the FACT-GOG-Neurotoxicity subscale, and a worst pain item from the Brief Pain Inventory. All patients who completed baseline quality-of-life assessments and at least one further follow-up assessment were evaluable for quality-of-life outcomes. This study is registered with ClinicalTrials.gov, number NCT00803062., Findings: Between April 6, 2009, and Jan 3, 2012, a total of 452 patients were enrolled in the trial, of whom 390 completed baseline quality-of-life assessment and at least one further assessment and were therefore evaluable for quality-of-life outcomes. In these patients, patient-reported outcome completion declined from 426 (94%) of 452 (at baseline) to 193 (63%) of 307 (9 months post-cycle 1), but completion rates did not differ significantly between treatment regimens (p=0·78). The baseline FACT-Cx TOI scores did not differ significantly between patients who received bevacizumab versus those who did not (p=0·27). Compared with patients who received chemotherapy alone, patients who received chemotherapy plus bevacizumab reported FACT-Cx TOI scores that were an average of 1·2 points lower (98·75% CI -4·1 to 1·7; p=0·30)., Interpretation: Improvements in overall survival and progression-free survival attributed to the incorporation of bevacizumab into the treatment of advanced cervical cancer were not accompanied by any significant deterioration in health-related quality of life. Patients responding to anti-angiogenesis therapy who maintain an acceptable quality of life could be suitable at progression for treatment with other novel therapies that might confer additional benefit., Funding: National Institutes of Health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To estimate quality-of-life (QOL)-adjusted cost-utility with addition of bevacizumab (B) to intravenous paclitaxel/carboplatin (PC) for primary treatment of advanced-stage epithelial ovarian cancer., Methods: A modified Markov state transition model of 3 regimens evaluated in GOG 218 (PC, PC+concurrent B [PCB], and PCB+maintenance B [PCB+B]) was populated by prospectively collected survival, adverse event, and QOL data from GOG 218. Progression-free survival (PFS) and overall survival (OS) were modeled using primary event data. Costs of grade 4 hypertension, grade 3-5 bowel events, and growth factor support were incorporated. QOL scores were converted to utilities and incorporated into the model. Monte Carlo probabilistic sensitivity analysis was performed to account for uncertainty in estimates., Results: PC was the least expensive ($4044) and least effective (mean 1.1 quality-adjusted progression-free years [QA-PFY]) regimen. PCB ($43,703 and 1.13 QA-PFY) was dominated by a combination of PC and PCB+B. PCB+B ($122,700 and 1.25 QA-PFY) was the most expensive regimen with an incremental cost-effectiveness ratio of $792,380/QA-PFY compared to PC. In a model not incorporating QOL, the incremental cost-effectiveness ratio (ICER) of PCB+B was $632,571/PFY compared to PC., Conclusions: In this cost-utility model, incorporation of QOL into an analysis of GOG 218 led to less favorable ICER (by >$150,000/QA-PFY) in regimens containing B compared with those that do not include B. Continued investigation of populations with ovarian cancer in whom the efficacy of treatment with bevacizumab is expected to be increased (or in whom QOL is expected to increase with use) is critical., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Chemosensitizing radiation with brachytherapy is standard of care for treatment of locally advanced cervical cancer, an increasingly rare disease. Treatment facility volume has been correlated with outcome in many diseases. Treatment outcome and likelihood of receiving standard therapy in locally advanced cervical cancer based on facility volume were examined using a large national cancer database., Methods: The National Cancer Data Base was queried for patients with stage IIB - IIIB cervical cancer from 1/1998 through 12/2010. Facility volumes were tallied. Overall survival was estimated using Kaplan-Meier method. Univariate and multivariable analyses were performed to determine variables affecting survival, receiving standard therapy, and total duration of radiotherapy., Results: We identified a total of 27,660 patients who were treated at 1361 facilities. Thirty of the facilities (2.2%) treated the highest quartile volume of patients (>9.4 patients annually) while 1072 facilities (78.8%) treated <2.4 patients annually. The median age of patients was 53, the majority were Caucasian, treated in a metropolitan area, and of squamous cell histology. Median survival of patients treated at lowest- and highest-volume centers were 42.3 months (95% CI 39.8-44.8) and 53.8 months (50.1-57.5), respectively (p < 0.001). The proportions of patients receiving brachytherapy and chemotherapy were 54.8% and 79.9%, respectively. On multivariable analysis, higher facility volume independently predicted improved survival (p = 0.022), increased likelihood of receiving brachytherapy (p < 0.0005) and chemotherapy (p = 0.013), and shorter time to radiotherapy completion (p < 0.0005)., Conclusions: Patients with locally advanced cervical cancer treated at high volume centers are more likely to receive standard therapy, complete therapy sooner, and experience better survival., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To determine if paclitaxel added to ifosfamide as first-line treatment for advanced uterine carcinosarcoma (CS) improves overall survival (OS), progression-free survival (PFS), response, and toxicity., Patients and Methods: Eligible patients had measurable stage III or IV, persistent, or recurrent uterine CS. Random assignment to treatment was between ifosfamide 2.0 g/m2 intravenously (IV) daily for 3 days (arm 1) or ifosfamide 1.6 g/m2 IV daily for 3 days plus paclitaxel 135 mg/m2 by 3-hour infusion day 1 (arm 2). Mesna was administered similarly (both arms); filgrastim began on day 4 (arm 2). Cycles were repeated every 21 days up to eight cycles., Results: Of 214 patients enrolled, 179 were eligible (arm 1, 91 patients; arm 2, 88 patients). Arm 2 patients experienced more frequent and severe sensory neuropathy (grade 1 to 4; 8% v 30%). The crude response rate was 29% (arm 1) and 45% (arm 2). The odds of response stratified by performance status were 2.21 greater in arm 2 (P = .017). Median PFS and OS, respectively, for arm 1 compared with arm 2 were 3.6 v 5.8 months and 8.4 v 13.5 months, respectively. There was a 31% decrease in the hazard of death (hazard ratio [HR], 0.69; 95% CI, 0.49 to 0.97; P = .03) and a 29% decrease in the hazard of progression (HR, 0.71; 95% CI, 0.51 to 0.97; P = .03) relative to arm 1 when stratifying by performance status., Conclusion: OS was significantly improved in arm 2, and toxicities were as expected and manageable. However, the need for active new agents persists, given that OS remains relatively poor in this disease.

Objective: To determine if smoking, a known risk factor for a number of cancers including cervical cancer, is associated with poor prognosis in patients with locally advanced cervical carcinoma treated with chemoradiation., Methods: Patients with primary, previously untreated, histologically confirmed stage II-B, III-B or IV-A cervical carcinoma participated in a Gynecologic Oncology Group (GOG) phase III study (GOG 165) and were randomly allocated to receive radiation plus either cisplatin or 5-fluorouracil. Smoking behavior was ascertained using an administered questionnaire and by quantifying urine cotinine concentration. Disease progression was defined as a >or=50% increase in the cross product of the existing tumor compared with previous assessments. Patients were followed until death., Results: Of 328 enrolled patients, 12 were ineligible, one was inevaluable for reported smoking status and 40 others were inevaluable for cotinine-derived smoking status. Among evaluable patients, 133 (42%) were reported smokers and 111 (40%) were cotinine-derived smokers. The kappa for agreement between the groups was 0.872 (P<0.01). Compared with non-smokers, median survival was 15 months shorter for reported smokers and 20 months shorter for cotinine-derived smokers (P<0.01). After adjusting for covariates, a significant increase in the risk of death (but not disease progression) was observed for reported smokers (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.01-2.27; P=0.04) and cotinine-derived smokers (HR: 1.57; 95% CI: 1.03-2.38; P=0.04)., Conclusions: Smoking predicts worse overall survival in women with locally advanced cervical carcinoma treated with chemoradiation.

Two virus-like particle human papillomavirus (HPV) vaccines have been shown to be nearly 100% effective in preventing type-specific persistent HPV infections and associated type-specific high-grade cervical intraepithelial neoplasia (CIN). Recently, it has been hypothesized that the administration of this vaccine to young girls in the United States might increase sexual promiscuity among adolescent women and/or young adults. Thus, it has been suggested that focused vaccine strategies either based on the risk of CIN or gender might be more rational or cost-effective. However, such strategies are unlikely to completely eradicate the burden of this disease and decrease the cost of cervical cancer screening. The suggestion that widespread vaccination will alter sexual practices is refuted and the rationale for the vaccination of all girls and boys is outlined.

Certification in Gynecologic Oncology and creation of the Society of Gynecologic Oncologists in the United States have led to the development of a specialty with individuals capable of performing complex abdominal and pelvic operations in the management of epithelial ovarian carcinoma. These operations can be divided into two types. 1) A staging operation to assess the extent of disease through careful palpation, histologic and cytologic assessment of all peritoneal surfaces along with removal of the uterus, ovaries and fallopian tubes, omentum, together with a bilateral pelvic and aortic lymphadenectomy. Such information allows the clinician to determine prognosis and if postoperative adjuvant therapy is indicated. 2) A debulking operation designed to resect or reduce the size of metastatic lesions as well as to remove the primary tumor including a bilateral salpingo-oophorectomy. This operation is designed to improve survival and cure. In spite of this apparently clear paradigm, there has been a steady debate as to the apparent justification of these operations, especially when the former is performed in a women who has not completed her childbearing and especially when the latter requires "ultraradical" procedures. Many feel that the pendulum is now swinging toward fertility-sparing surgery among young women with early invasive cancers and toward either neoadjuvant chemotherapy or less than ultraradical debulking among women with advanced ovarian cancer. The purpose of this study is not to provide an exhaustive review but rather to outline this debate and focus on the American experience with conservative surgery in the management of epithelial ovarian carcinoma.

Reimbursement for gynecologic oncologists can be categorized into three areas: payments for evaluation and management of clinical diagnosis, payments for chemotherapy, and reimbursement for surgical procedures. Revenue from surgical care is generally considered the major source of income for gynecologic oncologists. The transition to Medicare's resource-based relative value scale-based physician payment system began on January 1, 1992, culminating nearly a decade of effort by the medical profession and the government to change the way Medicare pays for physician services. The resource-based relative value scale payment schedule was fully phased in on January 1, 1996, and has been adopted by other third party payers. As a result of this reform, relative value units were created for current procedural technology codes and represent a composite of work, practice, and malpractice expenditures. When multiplied by a dollar conversion factor, relative value units can be used to calculate the reimbursement amount for all procedures covered by Medicare and other private insurers. Many of the discrepancies in reimbursement for similar procedures performed by gynecologists and urologists were partially corrected in 1997; however, sex-specific bias still exists in payment for surgical procedures performed on men and women.

Objective: To estimate the patterns of care and outcome of women with early cervical cancer in the United States based on surgical or radiation intent-to-treat principles., Methods: The Surveillance, Epidemiology, and End Results 1995 public-use file was the data source. Subjects between the ages of 15 and 80 years at diagnosis who were treated for stage Ib or IIa cervical cancer were identified. The 1039 women who comprised the study group were stratified according to age at diagnosis (40 years or less, older than 40 years), primary treatment intent (surgery, radiotherapy), tumor size (4 cm or less, over 4 cm), registry site, and ethnicity. Survival analyses included 784 women who had at least 2 years of follow-up., Results: There were 276 cancers (26.5%) over 4 cm, and 586 (56%) women were older than 40 years at diagnosis. There were 741 (71%) subjects in the surgical intent-to-treat group, and the remainder (298) were in the radiation intent-to-treat group. Kaplan-Meier analysis indicated a 5-year survival advantage for women with tumors 4 cm or less who were in the surgical intent-to-treat group compared with the radiation intent-to-treat group (86% and 71%, P <.001). Treatment group was not prognostic for cervical cancers over 4 cm (surgical intent-to-treat compared with radiation intent-to-treat; 72% and 68% survival, respectively). Multivariable analysis confirmed a survival advantage for women with surgical intent-to-treat and tumors of 4 cm or less., Conclusion: In the United States there is a survival advantage for surgical intent-to-treat compared with radiation intent-to-treat for women with tumors 4 cm or less, independent of ethnicity, adjuvant therapy, or age.