Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial

Frenel, JS; Kim, JW; Aryal, N; Asher, R; Berton, D; Vidal, L; Pautier, P; Ledermann, JA; Penson, RT; Oza, AM; Korach, J; Huzarski, T; Pignata, S; Colombo, N; Park-Simon, TW; Tamura, K; Sonke, GS; Freimund, AE; Lee, CK; Pujade-Lauraine, E

Author(s): Frenel, JS; Kim, JW; Aryal, N; Asher, R; Berton, D; Vidal, L; Pautier, P; Ledermann, JA; Penson, RT; Oza, AM; Korach, J; Huzarski, T; Pignata, S; Colombo, N; Park-Simon, TW; Tamura, K; Sonke, GS; Freimund, AE; Lee, CK; Pujade-Lauraine, E;
Details: Publication Year 2022-10,Volume 33,Issue #10,Page 1021-1028
Journal Title: Annals of Oncology
Publication Type: Research article
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.
Keywords: Adenosine Diphosphate/therapeutic use; *Antineoplastic Agents/therapeutic use; BRCA1 Protein/genetics; BRCA2 Protein/genetics; Carcinoma, Ovarian Epithelial/drug therapy/genetics; Disease Progression; Female; Humans; Maintenance Chemotherapy; Neoplasm Recurrence, Local/drug therapy/genetics; *Ovarian Neoplasms/drug therapy/genetics; Phthalazines; Piperazines; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use; Ribose/therapeutic use; BRCA mutation; PARP inhibitor resistance; relapsing ovarian cancer
Department(s): Medical Oncology
PubMed ID: 35772665
Publisher's Version: https://doi.org/10.1016/j.annonc.2022.06.011
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-10-25 06:46:38

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