Beryl L Manning-Geist1, Sushmita B Gordhandas1, Dilip D Giri2, Alexia Iasonos3, Qin Zhou4, Jeffrey Girshman5, Roisin E O'Cearbhaill6, Dmitriy Zamarin6, Stuart M Lichtman6, Paul J Sabbatini6, William P Tew6, Karen Li7, Autumn S McDonnell8, Emeline M Aviki9, Dennis S Chi9, Carol A Aghajanian6, Rachel N Grisham10. 1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA. 4. Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 5. Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 6. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA. 7. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 8. Research and Technology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 9. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA. 10. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA. Electronic address: grishamr@mskcc.org.
Abstract
OBJECTIVES: We sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-positive (AR+) ovarian cancer. METHODS: This was a single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1-3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013-7/2018. Following consent, archival tissue was evaluated for AR+. Enrolled patients received daily enzalutamide 160 mg until progression of disease or treatment discontinuation. Adverse events were graded by CTCAE v4.0. Co-primary endpoints were 6-month progression-free survival (PFS6) and overall response rate (ORR) by RECIST 1.1 criteria. RESULTS: During the study period, 160 patients were screened and 59 (45 high-grade serous [HGS] and 14 low-grade serous [LGS]) consented to treatment on study. There was 1 confirmed and 1 unconfirmed partial response. The ORR was 1.7% (90% CI: 0.2-100%). The overall PFS6 rate (as binary) was 22% (90% CI: 15.1-100%). The 6-month PFS rate (as time to event) was 19.8% for HGS patients (90% CI: 12.7-100%) and 38.5% (90% CI: 21.7%-100%) for LGS patients. Grade 3 toxicities occurred in 6 patients (one toxicity (Grade 3 rash) was considered a dose-limiting toxicity). One patient died of cardiac arrest after 42 days on treatment of a cardiac arrest not attributed to study drug. CONCLUSIONS: The study met its primary endpoint, with a PFS6 rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients.
OBJECTIVES: We sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-positive (AR+) ovarian cancer. METHODS: This was a single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1-3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013-7/2018. Following consent, archival tissue was evaluated for AR+. Enrolled patients received daily enzalutamide 160 mg until progression of disease or treatment discontinuation. Adverse events were graded by CTCAE v4.0. Co-primary endpoints were 6-month progression-free survival (PFS6) and overall response rate (ORR) by RECIST 1.1 criteria. RESULTS: During the study period, 160 patients were screened and 59 (45 high-grade serous [HGS] and 14 low-grade serous [LGS]) consented to treatment on study. There was 1 confirmed and 1 unconfirmed partial response. The ORR was 1.7% (90% CI: 0.2-100%). The overall PFS6 rate (as binary) was 22% (90% CI: 15.1-100%). The 6-month PFS rate (as time to event) was 19.8% for HGS patients (90% CI: 12.7-100%) and 38.5% (90% CI: 21.7%-100%) for LGS patients. Grade 3 toxicities occurred in 6 patients (one toxicity (Grade 3 rash) was considered a dose-limiting toxicity). One patient died of cardiac arrest after 42 days on treatment of a cardiac arrest not attributed to study drug. CONCLUSIONS: The study met its primary endpoint, with a PFS6 rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients.
Authors: Anthony Bonaventura; Rachel L OʼConnell; Cristina Mapagu; Philip J Beale; Orla M McNally; Linda R Mileshkin; Peter T Grant; Alison M Hadley; Jeffery C H Goh; Katrin M Sjoquist; Julie Martyn; Anna DeFazio; James Scurry; Michael L Friedlander Journal: Int J Gynecol Cancer Date: 2017-06 Impact factor: 3.437
Authors: Lauren A Baldwin; Bin Huang; Rachel W Miller; Thomas Tucker; Scott T Goodrich; Iwona Podzielinski; Christopher P DeSimone; Fred R Ueland; John R van Nagell; Leigh G Seamon Journal: Obstet Gynecol Date: 2012-09 Impact factor: 7.661
Authors: Juliet Richards; Ai Chiin Lim; Colin W Hay; Angela E Taylor; Anna Wingate; Karolina Nowakowska; Carmel Pezaro; Suzanne Carreira; Jane Goodall; Wiebke Arlt; Iain J McEwan; Johann S de Bono; Gerhardt Attard Journal: Cancer Res Date: 2012-03-12 Impact factor: 12.701
Authors: Susana Banerjee; Holly Tovey; Rebecca Bowen; Elizabeth Folkerd; Lucy Kilburn; Jennifer McLachlan; Marcia Hall; Nina Tunariu; Ayoma Attygalle; Joao Paulo Da Silveira Nogueira Lima; Sophie Perry; Peter Chatfield; Margaret Hills; Stan Kaye; Gert Attard; Mitch Dowsett; Judith M Bliss Journal: Ther Adv Med Oncol Date: 2020-12-29 Impact factor: 8.168
Authors: Ian Krop; Vandana Abramson; Marco Colleoni; Tiffany Traina; Frankie Holmes; Laura Garcia-Estevez; Lowell Hart; Ahmad Awada; Claudio Zamagni; Patrick G Morris; Lee Schwartzberg; Stephen Chan; Ayca Gucalp; Laura Biganzoli; Joyce Steinberg; Lorenzo Sica; Maureen Trudeau; Denka Markova; Jamal Tarazi; Zhou Zhu; Thomas O'Brien; Catherine M Kelly; Eric Winer; Denise A Yardley Journal: Clin Cancer Res Date: 2020-09-28 Impact factor: 12.531