Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study

Drew, Y. et al. (2024) Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study. Clinical Cancer Research, 30(1), pp. 50-62. (doi: 10.1158/1078-0432.ccr-23-2249) (PMID:37939124) (PMCID:PMC10767301)

Abstract

Purpose: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). Patients and Methods: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). Results: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1–97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5–43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2–86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. Conclusions: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified.

• Item Type: Articles
• Additional Information: ** Article version: VoR ** From Crossref journal articles via Jisc Publications Router ** History: epub 08-11-2023; issued 08-11-2023; ppub 05-01-2024. ** Licence for VoR version of this article starting on 05-01-2024: https://creativecommons.org/licenses/by-nc-nd/4.0/
• Keywords: Cancer Research, Oncology
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Roxburgh, Professor Patricia

Creator Roles

Roxburgh, P.: Investigation, Resources, Writing – original draft, Writing – review and editing

• Authors: Drew, Y., Kim, J.-W., Penson, R. T., O'Malley, D. M., Parkinson, C., Roxburgh, P., Plummer, R., Im, S.-A., Imbimbo, M., Ferguson, M., Rosengarten, O., Steeghs, N., Kim, M. H., Gal-Yam, E., Tsoref, D., Kim, J.-H., You, B., De Jonge, M., Lalisang, R., Gort, E., Bastian, S., Meyer, K., Feeney, L., Baker, N., Ah-See, M.-L., Domchek, S. M., and Banerjee, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Clinical Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 1078-0432
• ISSN (Online): 1557-3265
• Published Online: 08 November 2023
• Copyright Holders: Copyright © 2023 The Author(s)
• First Published: First published in Clinical Cancer Research 30:50-62
• Publisher Policy: Reproduced under a creative commons licence