J S Frenel1, J W Kim2, N Aryal3, R Asher3, D Berton4, L Vidal5, P Pautier6, J A Ledermann7, R T Penson8, A M Oza9, J Korach10, T Huzarski11, S Pignata12, N Colombo13, T W Park-Simon14, K Tamura15, G S Sonke16, A E Freimund17, C K Lee3, E Pujade-Lauraine18. 1. Institut de Cancerologie de l'Ouest, GINECO, GINEGEPS, Centre René Gauducheau, Saint-Herblain, France. Electronic address: jean-sebastien.frenel@ico.unicancer.fr. 2. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea. 3. NHMRC CTC Centre, University of Sydney, Camperdown, Sydney, Australia. 4. Institut de Cancerologie de l'Ouest, GINECO, GINEGEPS, Centre René Gauducheau, Saint-Herblain, France. 5. GEICO & H Clínic de Barcelona, Barcelona, Spain. 6. GINECO & Gustave Roussy Cancer Center, Villejuif, France. 7. NCRI & University College London, London, UK. 8. Massachusetts General Hospital, Boston, USA. 9. Princess Margaret Cancer Centre, Toronto, Canada. 10. ISGO & Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. 11. Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. 12. MITO & Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale Napoli, Naples, Italy. 13. MaNGO & European Institute of Oncology IRCCS and University of Milan-Bicocca, Milano, Italy. 14. AGO & Medical School, Department of Gynecologic Oncology, Hannover, Hannover, Germany. 15. Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 16. DGOG & Netherlands Cancer Institute, Amsterdam, Netherlands. 17. Peter MacCallum Cancer Centre, Melbourne, Australia. 18. ARCAGY-GINECO, Paris, France.
Abstract
BACKGROUND: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. PATIENTS AND METHODS: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. RESULTS: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). CONCLUSIONS: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research.
BACKGROUND: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. PATIENTS AND METHODS: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. RESULTS: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). CONCLUSIONS: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research.
Authors: Ignace Vergote; Antonio Gonzalez-Martin; Domenica Lorusso; Charlie Gourley; Mansoor Raza Mirza; Jean-Emmanuel Kurtz; Aikou Okamoto; Kathleen Moore; Frédéric Kridelka; Iain McNeish; Alexander Reuss; Bénédicte Votan; Andreas du Bois; Sven Mahner; Isabelle Ray-Coquard; Elise C Kohn; Jonathan S Berek; David S P Tan; Nicoletta Colombo; Rongyu Zang; Nicole Concin; Dearbhaile O'Donnell; Alejandro Rauh-Hain; C Simon Herrington; Christian Marth; Andres Poveda; Keiichi Fujiwara; Gavin C E Stuart; Amit M Oza; Michael A Bookman Journal: Lancet Oncol Date: 2022-08 Impact factor: 54.433