Nobuaki Matsubara1, Kazuo Nishimura2, Satoru Kawakami3, Jae Young Joung4, Hiroji Uemura5, Takayuki Goto6, Tae Gyun Kwon7, Mikio Sugimoto8, Masashi Kato9, Shian-Shiang Wang10, See-Tong Pang11, Chung-Hsin Chen12, Tomoko Fujita13, Masahiro Nii13, Liji Shen14, Melanie Dujka15, Maha Hussain16, Johann de Bono17. 1. National Cancer Center Hospital East, Chiba, Japan. 2. Osaka International Cancer Institute, Osaka, Japan. 3. Saitama Medical University Saitama Medical Center, Saitama, Japan. 4. National Cancer Center, Goyang-si, South Korea. 5. Yokohama City University Medical Center, Yokohama, Japan. 6. Department of Urology, Kyoto University Hospital, Kyoto, Japan. 7. Chilgok Kyungpook National University Medical Center, Daegu, South Korea. 8. Department of Urology, Kagawa University Hospital, Kagawa, Japan. 9. Department of Urology, Nagoya University Hospital, Nagoya, Japan. 10. Division of Urology, Department of Surgery, Veterans General Hospital Taichung, Taichung, Taiwan. 11. Department of Uro-oncology, Chang Gung Medical Foundation-LinKou Branch, Taoyuan City, Taiwan. 12. Department of Urology, National Taiwan University Hospital, Taipei, Taiwan. 13. AstraZeneca, Osaka, Japan. 14. Merck & Co., Inc., Kenilworth, NJ, USA. 15. AstraZeneca, Gaithersburg, MD, USA. 16. Division of Hematology-Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 17. Drug Development Unit, Institute of Cancer Research and Royal Marsden Hospital, London, UK.
Abstract
BACKGROUND: The Phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control; randomized 2:1 to olaparib or control) in men with homologous recombination repair gene alterations and metastatic castration-resistant prostate cancer whose disease progressed on prior next-generation hormonal agent. METHODS: We present efficacy and safety data from an exploratory post hoc analysis of olaparib in the PROfound Asian subset. Analyses were not planned, alpha controlled or powered. Of 101 Asian patients enrolled in Japan (n=57), South Korea (n=29) and Taiwan (n=15), 66 and 35 patients received olaparib and control, respectively. RESULTS: Radiographic progression-free survival (rPFS) and overall survival (OS) favored olaparib versus control in Cohort A [rPFS 7.2 vs. 4.5 months, HR 0.58, 95% CI 0.29-1.21, P = 0.14 (nominal); OS 23.4 vs. 17.8 months, HR 0.81, 95% CI 0.40-1.74, P = 0.57 (nominal)] and Cohorts A+B [rPFS 5.8 vs. 3.5 months, HR 0.69, 95% CI 0.42-1.16, P = 0.13 (nominal); OS 18.6 vs. 16.2 months, HR 0.96, 95% CI 0.56-1.70, P = 0.9 (nominal)]. Olaparib showed greatest improvement in patients harboring BRCA alterations [rPFS 9.3 vs. 3.5 months, HR 0.17, 95% CI 0.06-0.49, P = 0.0003 (nominal); OS 26.8 vs. 14.3 months, HR 0.62, 95% CI 0.24-1.79, P = 0.34 (nominal)]. Safety data were consistent with the known profile of olaparib, with no new safety signals identified. CONCLUSION: In PROfound, there was a statistically significant improvement in outcomes reported in the global population of patients with metastatic castration-resistant prostate cancer and alterations in homologous recombination repair genes whose disease progressed on prior next-generation hormonal agent compared with control. For the subset of Asian patients reported here, exploratory analysis suggested that there was also an improvement in outcomes versus control. The safety and tolerability of olaparib in Asian patients were similar to that of the PROfound global population. CLINICAL TRIAL NUMBER: ClinicalTrials.gov NCT02987543.
BACKGROUND: The Phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control; randomized 2:1 to olaparib or control) in men with homologous recombination repair gene alterations and metastatic castration-resistant prostate cancer whose disease progressed on prior next-generation hormonal agent. METHODS: We present efficacy and safety data from an exploratory post hoc analysis of olaparib in the PROfound Asian subset. Analyses were not planned, alpha controlled or powered. Of 101 Asian patients enrolled in Japan (n=57), South Korea (n=29) and Taiwan (n=15), 66 and 35 patients received olaparib and control, respectively. RESULTS: Radiographic progression-free survival (rPFS) and overall survival (OS) favored olaparib versus control in Cohort A [rPFS 7.2 vs. 4.5 months, HR 0.58, 95% CI 0.29-1.21, P = 0.14 (nominal); OS 23.4 vs. 17.8 months, HR 0.81, 95% CI 0.40-1.74, P = 0.57 (nominal)] and Cohorts A+B [rPFS 5.8 vs. 3.5 months, HR 0.69, 95% CI 0.42-1.16, P = 0.13 (nominal); OS 18.6 vs. 16.2 months, HR 0.96, 95% CI 0.56-1.70, P = 0.9 (nominal)]. Olaparib showed greatest improvement in patients harboring BRCA alterations [rPFS 9.3 vs. 3.5 months, HR 0.17, 95% CI 0.06-0.49, P = 0.0003 (nominal); OS 26.8 vs. 14.3 months, HR 0.62, 95% CI 0.24-1.79, P = 0.34 (nominal)]. Safety data were consistent with the known profile of olaparib, with no new safety signals identified. CONCLUSION: In PROfound, there was a statistically significant improvement in outcomes reported in the global population of patients with metastatic castration-resistant prostate cancer and alterations in homologous recombination repair genes whose disease progressed on prior next-generation hormonal agent compared with control. For the subset of Asian patients reported here, exploratory analysis suggested that there was also an improvement in outcomes versus control. The safety and tolerability of olaparib in Asian patients were similar to that of the PROfound global population. CLINICAL TRIAL NUMBER: ClinicalTrials.gov NCT02987543.
Authors: Wassim Abida; Joshua Armenia; Anuradha Gopalan; Ryan Brennan; Michael Walsh; David Barron; Daniel Danila; Dana Rathkopf; Michael Morris; Susan Slovin; Brigit McLaughlin; Kristen Curtis; David M Hyman; Jeremy C Durack; Stephen B Solomon; Maria E Arcila; Ahmet Zehir; Aijazuddin Syed; Jianjiong Gao; Debyani Chakravarty; Hebert Alberto Vargas; Mark E Robson; Vijai Joseph; Kenneth Offit; Mark T A Donoghue; Adam A Abeshouse; Ritika Kundra; Zachary J Heins; Alexander V Penson; Christopher Harris; Barry S Taylor; Marc Ladanyi; Diana Mandelker; Liying Zhang; Victor E Reuter; Philip W Kantoff; David B Solit; Michael F Berger; Charles L Sawyers; Nikolaus Schultz; Howard I Scher Journal: JCO Precis Oncol Date: 2017-05-31
Authors: Philipp Nuhn; Johann S De Bono; Karim Fizazi; Stephen J Freedland; Maurizio Grilli; Philip W Kantoff; Guru Sonpavde; Cora N Sternberg; Srinivasan Yegnasubramanian; Emmanuel S Antonarakis Journal: Eur Urol Date: 2018-04-16 Impact factor: 20.096
Authors: Johann de Bono; Joaquin Mateo; Karim Fizazi; Fred Saad; Neal Shore; Shahneen Sandhu; Kim N Chi; Oliver Sartor; Neeraj Agarwal; David Olmos; Antoine Thiery-Vuillemin; Przemyslaw Twardowski; Niven Mehra; Carsten Goessl; Jinyu Kang; Joseph Burgents; Wenting Wu; Alexander Kohlmann; Carrie A Adelman; Maha Hussain Journal: N Engl J Med Date: 2020-04-28 Impact factor: 91.245
Authors: Maha Hussain; Joaquin Mateo; Karim Fizazi; Fred Saad; Neal Shore; Shahneen Sandhu; Kim N Chi; Oliver Sartor; Neeraj Agarwal; David Olmos; Antoine Thiery-Vuillemin; Przemyslaw Twardowski; Guilhem Roubaud; Mustafa Özgüroğlu; Jinyu Kang; Joseph Burgents; Christopher Gresty; Claire Corcoran; Carrie A Adelman; Johann de Bono Journal: N Engl J Med Date: 2020-09-20 Impact factor: 91.245