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1. PARPi after PARPi in epithelial ovarian cancer

Author

K.G. Essel, K. Behbakht, T. Lai, L. Hand, E. Evans, J. Dvorak, K. Ding, G. Konecny, and K.N. Moore

Subjects
PARP inhibitor, Ovarian cancer, Gynecology and obstetrics, RG1-991, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The objective of this study was to describe the treatment experience of patients with recurrent epithelial ovarian cancer who are retreated with an inhibitor of poly(ADP-ribose)-polymerase (PARPi). We conducted a multi-institutional, retrospective review of ovarian cancer patients who received ≥2 lines of therapy containing a PARPi. Demographic, clinical, and pathological data were analyzed with descriptive statistics. Twenty-two patients were identified. For initial PARPi (PARPi1), 12 patients (54.5%) received veliparib, 7 (31.8%) olaparib and 3 (13.6%) rucaparib resulting in 10 patients who had no evidence of disease at the completion of therapy (NED), 3 partial responses (PR), 4 stable disease (SD), and 3 progressive disease (PD). (All 10 CRs involved veliparib given in conjunction with cytotoxic chemotherapy). PARPi1 was used as maintenance in 2 patients. PARPi1 was discontinued because planned number of cycles was reached (n = 10), progression (n = 8), toxicity (n = 2), other (n = 2). For second PARPi (PARPi2), 10 patients (45.4%) received niraparib, 6 (27.3%) olaparib, and 6 (27.3%) rucaparib resulting in 3 PR, 13 SD, and 3 PD. PARPi2 was used as maintenance in 3 patients. The 3 patients who experienced a PR to PARPi2 had a BRCA mutation and were NED following PARPi1. PARPi2 was discontinued because of progression (n = 13), toxicity (n = 6), other (n = 2). One patient currently remains on PARPi2. Toxicity after PARPi1 was not associated with toxicity from PARPi2 (p > 0.05). With 3 approved PARPi for different indications including frontline and recurrence, the opportunity to reuse PARPi has increased. Characterizing those who should be re-challenged is an important initiative moving forward.

Published
2021
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2. Imaging biomarkers of adiposity and sarcopenia as potential predictors for overall survival among patients with endometrial cancer treated with bevacizumab

Author

J. Gillen, K.A. Mills, J. Dvorak, B. Zheng, T. Thai, R. Salani, C.M. Cosgrove, B. Davidson, P.H. Thaker, and K.N. Moore

Subjects
Gynecology and obstetrics, RG1-991, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Objective: To examine associations of body mass index (BMI), subcutaneous fat area (SFA) and density (SFD), visceral fat area (VFA) and density (VFD) and total psoas area (TPA) to outcomes among patients receiving chemotherapy with or without bevacizumab for advanced or recurrent endometrial cancer (EC). Methods: This was a multi-institutional, retrospective study of patients with EC treated with and without bevacizumab as part of front-line, platinum based chemotherapy. Demographics and clinical characteristics were collected. SFA, VFA, SFD, VFD, and TPA were determined from pre-treatment CT scans using a deep learning algorithm. Data was compared with overall survival (OS) and progression free survival (PFS). Results: Seventy-eight patients were analyzed. The majority were Caucasian (87.2%) with a mean BMI of 34.7 kg/m2. PFS and OS did not differ between patients with BMI, SFA, VFA, SFD, VFD, or TPA ≥ the 50th percentile compared to

Published
2019
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3. Tumor lysis syndrome in gynecologic cancers: An uncommon but important diagnosis to recognize

Author

T. Castellano, B.A. Bulard, A. Staley, and K.N. Moore

Subjects
Gynecology and obstetrics, RG1-991, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Objectives: To describe the incidence, treatment and outcomes associated with tumor lysis syndrome (TLS) in women with gynecologic cancer (GOC). Methods: A retrospective multi-institutional review of TLS associated with GOC. Women presenting with an elevated serum uric acid managed with intravenous (IV) rasburicase were included. Descriptive statistics of patient demographics, clinical findings, and outcome data was completed. Results: From two large academic institutions N = 18 patients were found to meet inclusion criteria from 2008 to 2018, reflecting an approximate 5% incidence of clinically treated TLS associated with GOC in our cohort. Median age was 60 years, a majority were Caucasian (n = 11, 61.1%), median BMI was 36.2. TLS was associated with a high-grade GOC in n = 17 (94.4%) cases. TLS was commonly diagnosed with a new GOC (n = 12, 70.6%) and following receipt of chemotherapy in n = 9 (50.0%) cases. Six (66.7%) patients were treated with paclitaxel or combination, five (55.5%) with a platinum or combination, and two (22.2%) with a CD47 inhibitor. Chief complaints included electrolyte and renal abnormalities (n = 11, 73.3%). Peak serum uric acid, potassium, creatinine and phosphorus levels were 14.1 mg/dL, 5.7 mEq/L, 5.1 mg/dL, and 6.8 mg/dL, respectively. Nine patients received hospice during their admission with 3 (20%) deaths occurring as inpatients. There were 12 deaths with median OS of 16 d (range: 2–87 d). Conclusions: Though rare, TLS can be associated with GOC. Early recognition of presenting symptoms, laboratory findings and expedited treatment may help with electrolyte recovery; however, TLS associated with GOC may herald a rapidly deteriorating state with significant associated mortality. Keywords: Tumor lysis syndrome, Rasburicase, Gynecologic oncology

Published
2019
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6. A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium

Author

C.G. Jackson, K.N. Moore, L. Cantrell, B.K. Erickson, L.R. Duska, D.L. Richardson, L.M. Landrum, L.L. Holman, J.L. Walker, R.S. Mannel, K.M. Moxley, L. Queimado, A. Cohoon, K. Ding, and L.E. Dockery

Subjects
Bevacizumab, Endometrium, Indoles, Oncology, Antineoplastic Combined Chemotherapy Protocols, Obstetrics and Gynecology, Humans, Uterine Cervical Neoplasms, Female, Cervix Uteri, Neoplasm Recurrence, Local, Endometrial Neoplasms
Abstract

The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer.Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival.Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib.The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen.

Published
2021

9. 197TiP First-in-human (FIH) phase I/II study of ubamatamab, a MUC16xCD3 bispecific antibody, administered alone or in combination with cemiplimab in patients with recurrent ovarian cancer (OC)

Author

K.N. Moore, S. Bouberhan, E. Hamilton, J. Liu, R.E. O'Cearbhaill, D. O'Malley, K. Papadimitriou, D. Schröder, E. Van Nieuwenhuysen, S-Y. Yoo, M. Peterman, P. Goncalves, T. Schmidt, M. Zhu, I. Lowy, T. Uldrick, and E.A. Miller

Subjects
Oncology, Immunology and Allergy
Published
2022
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11. 523MO Ubamatamab (REGN4018, MUC16xCD3 bispecific antibody) monotherapy in patients with recurrent ovarian cancer (OC): Phase I dose-escalation analysis

Author

E. Van Nieuwenhuysen, D. O'Malley, R.E. O'Cearbhaill, K.N. Moore, E.P. Hamilton, O. Yeku, S. Bouberhan, J.Y. Hou, S-Y. Yoo, J. Brouwer-Visser, H.K. Cheung, M. Peterman, P. Goncalves, T. Schmidt, M. Zhu, I. Lowy, T. Rowlands, T.S. Uldrick, E.A. Miller, and J.F. Liu

Subjects
Oncology, Hematology
Published
2022
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13. 517O Overall survival (OS) at 7-year (y) follow-up (f/u) in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) who received maintenance olaparib in the SOLO1/GOG-3004 trial

Author

P. DiSilvestro, S. Banerjee, N. Colombo, G. Scambia, B-G. Kim, A. Oaknin, M.L. Friedlander, A.S. Lisyanskaya, A. Floquet, A. Leary, G.S. Sonke, C. Gourley, A.M. Oza, A.J. Gonzalez Martin, C. Aghajanian, W.H. Bradley, C. Mathews, J. McNamara, E. Lowe, and K.N. Moore

Subjects
Oncology, Hematology
Published
2022
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14. 520MO Safety and efficacy of nivolumab (NIVO) ± ipilimumab (IPI) in patients (pts) with recurrent/metastatic cervical cancer (R/M Cx Ca) in checkmate 358

Author

A. Oaknin, K.N. Moore, T. Meyer, J.L. González, L. Devriese, A. Amin, C.D. Lao, V. Boni, W.H. Sharfman, J.C. Park, M. Tahara, S.L. Topalian, M.E. Magallanes Maciel, A. Molina Alavez, A. Khan, C. Copigneaux, M. Lee, C. Garnett-Benson, X. Wang, and R.W. Naumann

Subjects
Oncology, Hematology
Published
2022
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15. 164P Preliminary results from a phase I/II study of BDC-1001, a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), in patients (pts) with advanced HER2-expressing solid tumors

Author

M.R. Sharma, R.D. Carvajal, G.J. Hanna, Y.K. Kang, J. Lee, K.W. Lee, B.T. Li, K.N. Moore, M. Pegram, D. Rasco, A. Spira, D. Wang, B.A. Weinberg, M. Alonso, L. Fang, A. Husain, M. Kowanetz, E.A. Perez, and E.I. Dumbrava

Subjects
Oncology, Hematology
Published
2021
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19. Tolerability and adverse events experienced by women with ovarian cancer treated with intravenous or intraperitoneal chemotherapy plus veliparib and bevacizumab based on BRCA status

Author

J. Gillen, A. Miller, K.N. Moore, K.M. Bell-McGuinn, R. Schilder, J.L. Walker, W.E. Brady, R.E. O'Cearbhaill, S.R. Guntupalli, D.K. Armstrong, A.R. Hagemann, H.J. Gray, L.R. Duska, C.A. Mathews, A. Chen, D.M. O'Malley, S.W. Gordon, P.M. Fracasso, and C. Aghajanian

Subjects
Oncology, Obstetrics and Gynecology
Published
2020
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28. Patient-centred outcomes with maintenance olaparib in newly diagnosed patients with advanced ovarian cancer (OC) and a BRCA mutation in the phase III SOLO1 trial to support the clinical benefit of prolongation of progression-free survival (PFS)

Author

M.L. Friedlander, K.N. Moore, N. Colombo, G. Scambia, B.-G. Kim, A. Oaknin, A. Lisyanskaya, A. Floquet, A. Leary, G.S. Sonke, C. Gourley, S. Banerjee, A. Oza, A. González-Martín, C. Aghajanian, W. Bradley, E. Lowe, R. Hettle, E. Flood, and P. Disilvestro

Subjects
Oncology, Hematology
Published
2019
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32. Urinary incontinence after radical prostatectomy: a randomized controlled trial comparing pelvic muscle exercises with or without electrical stimulation

Author

A. Hughton, D. Griffiths, and K.N. Moore

Subjects
medicine.medical_specialty, Pelvic floor, business.industry, Prostatectomy, Urology, medicine.medical_treatment, Standard treatment, Urinary incontinence, Urinary catheterization, law.invention, Surgery, Neck of urinary bladder, medicine.anatomical_structure, Randomized controlled trial, law, medicine, medicine.symptom, business, Radical retropubic prostatectomy
Abstract

Objectives To assess the effectiveness of intensive conservative treatment on and the impact of urinary incontinence after radical retropubic prostatectomy. Patients and methods Sixty-three men with urinary incontinence ≥ 8 weeks after radical prostatectomy were randomized to one of three groups; group 1, standard treatment (control); group 2, intensive pelvic muscle exercises (PME); or group 3, PME plus electrical stimulation (PME+ES). Group 1 received verbal and written instructions about postoperative PME from their urologist and from the nurses at the pre-admission clinic. Groups 2 and 3 were treated by a physiotherapist for 30 min twice a week for 12 weeks and carried out home exercises three times a day on the days when they were not treated. Outcome was assessed using the 24-h pad test, two validated quality-of-life questionnaires and a urine symptom inventory, all obtained at baseline, 12, 16 and 24 weeks after enrolment. The final pad test was carried out ≈8 months after surgery. Results Fifty-eight patients completed the study, 21 in group 1, 18 in group 2 and 19 in group 3; five discontinued, three with bladder neck contractures requiring dilatation, one with rectal pain when doing the exercises and one unable to complete therapy while on vacation. The mean (median) time elapsed from surgery to entry into the study was 19 (8) weeks. At 12 weeks from baseline, the mean overall urine loss had decreased from 463 g to 115 g but there were no differences among groups, nor were there significant differences in urine loss at 16 and 24 weeks (F=0.16, P=0.69). There was a significant impact on quality of life during the early recovery. Despite preoperative instructions, many patients revealed little or no knowledge about catheter care, bladder spasms, rectal pain, incontinence and erectile dysfunction. Little of the preoperative education was retained because of the overwhelming nature of the diagnosis. Conclusions From the initial assessment to the final pad-test at ≈8 months after surgery, incontinence improved greatly in all three groups. This rapid improvement may have masked any treatment benefit. Further research should address incontinence in men whose urine loss has stabilized and who underwent surgery >8 months previously. Moreover, a telephone-based follow-up soon after discharge may alleviate many of the concerns expressed.

Published
2008
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35. Measurement of the decay rate and form factor parameter in the decay KL→e+e−γ

Author

H.G. Becker, Cristina Biino, Ivan Mikulec, Vladimir Kekelidze, R. Turlay, M. Holder, D. Marras, G. Fischer, A. Gonidec, A. I. Zinchenko, Michael Ziolkowski, S. Luitz, I. Potrebenikov, Anton Taurok, G. Collazuol, M. Sozzi, S. A. Wotton, E. Iacopini, G. Govi, Konrad Kleinknecht, S. Schanne, A. Gianoli, Paolo Calafiura, Matthew Needham, B. Vallage, P. Grafström, R.W. Moore, I. Mannelli, J. Nassalski, R. Granier de Cassagnac, A. Lai, Andrea Formica, G. Kesseler, J.B. Cheze, M. Cirilli, Niels Doble, W. Kubischta, Michal Szleper, O. Boyle, P. F. Dalpiaz, A. Nappi, P. Hristov, P. Lubrano, P. Debu, R. Fantechi, H. D. Wahl, Giacomo Graziani, A. Mestvirishvili, M. Savrie, U. Koch, A. Winhart, Louis Fayard, G. Neuhofer, F. Marchetto, J. C. Chollet, F. Costantini, D. J. Munday, Milene Calvetti, H. Blümer, L. Köpke, M. Bender, I.G. Knowles, P. Buchholz, E. Menichetti, A. Kalter, B. Peyaud, M. Martini, Lydia Iconomidou-Fayard, D. Schinzel, J. Scheidt, B. Hay, Victoria Jane Martin, W. Wislicki, Michael Andrew Parker, S. Giudici, M. De Beer, E. Rondio, H. Dibon, J. Ocariz, Roberta Arcidiacono, G.D. Barr, H. Taureg, B. Renk, Augusto Ceccucci, S. Wronka, Mayda Velasco, V. Fanti, I. Wingerter, V. Schönharting, G. Tatishvili, O. Vossnack, Lau Gatignon, Benedetto Gorini, G. Unal, M. Porcu, A. Tkatchev, M. Pepe, D. Coward, Manfred Jeitler, J.P. Matheys, C. Cerri, J. Schmidt, Luciano Musa, G. Bocquet, I. Augustin, K.N. Moore, J. Duclos, Andrea Bizzeti, P. Cenci, J. Bremer, G. Anzivino, A. Norton, M. Pernicka, C. Ebersberger, G. Wirrer, D. Vattolo, S. Crépé, E. Mazzucato, M. Markytan, M. Lenti, H. Fox, A. Lacourt, R. Wilhelm, B. Panzer-Steindel, Fabrizio Petrucci, P.L. Frabetti, T. O. White, H. Parsons, Sandro Palestini, A. Michetti, Wolfgang Funk, R. Carosi, D.C. Cundy, Y. Schué, G.M. Pierazzini, M. Wittgen, and J. Cogan

Subjects
Pseudoscalar, Physics, Nuclear physics, Nuclear and High Energy Physics, Amplitude, Meson, Branching fraction, Form factor (quantum field theory), Alpha (ethology), Relative strength
Abstract

The decay rate of the neutral K meson KL→e+e−γ has been measured with the NA48 detector at the CERN SPS. A total of 6864 events has been observed with an estimated background of 10 events. The branching ratio is Γ(KL→e+e−γ)/Γ(KL→all) = (1.06±0.02stat±0.02sys±0.04calc)×10−5. The parameter α K ∗ describing the relative strength of the two contributing amplitudes to this decay through intermediate pseudoscalar or vector mesons was measured to be α K ∗ =−0.36±0.06stat±0.02sys.

Published
1999
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