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Multicenter Study
. 2023 May:172:121-129.
doi: 10.1016/j.ygyno.2023.03.019. Epub 2023 Apr 6.

Maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer: Outcomes by somatic and germline BRCA and other homologous recombination repair gene mutation status in the ORZORA trial

Sandro Pignata  1 , Amit Oza  2 , Geoff Hall  3 , Beatriz Pardo  4 , Radoslaw Madry  5 , David Cibula  6 , Jaroslav Klat  7 , Ana Montes  8 , Rosalind Glasspool  9 , Nicoletta Colombo  10 , Imre Pete  11 , Ana Herrero Ibáñez  12 , Margarita Romeo Marín  13 , Rumyana Ilieva  14 , Constanta Timcheva  15 , Massimo Di Maio  16 , Christopher Blakeley  17 , Rosie Taylor  17 , Alan Barnicle  17 , Andrew Clamp  18
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Free article
Multicenter Study

Maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer: Outcomes by somatic and germline BRCA and other homologous recombination repair gene mutation status in the ORZORA trial

Sandro Pignata et al. Gynecol Oncol. 2023 May.
Free article

Abstract

Background: The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment.

Methods: Patients received maintenance olaparib capsules (400 mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort. The co-primary endpoints were investigator-assessed progression-free survival (PFS; modified Response Evaluation Criteria in Solid Tumors v1.1) in BRCAm and sBRCAm cohorts. Secondary endpoints included health-related quality of life (HRQoL) and tolerability.

Results: 177 patients received olaparib. At the primary data cut-off (17 April 2020), the median follow-up for PFS in the BRCAm cohort was 22.3 months. The median PFS (95% CI) in BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts was 18.0 (14.3-22.1), 16.6 (12.4-22.2), 19.3 (14.3-27.6) and 16.4 (10.9-19.3) months, respectively. Most patients with BRCAm reported improvements (21.8%) or no change (68.7%) in HRQoL and the safety profile was as expected.

Conclusions: Maintenance olaparib had similar clinical activity in PSR OC patients with sBRCAm and those with any BRCAm. Activity was also observed in patients with a non-BRCA HRRm. ORZORA further supports use of maintenance olaparib in all patients with BRCA-mutated, including sBRCA-mutated, PSR OC.

Keywords: BRCA mutation; HRR; Maintenance; Olaparib; Ovarian cancer.

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Conflict of interest statement

Declaration of Competing Interest Sandro Pignata: Honoraria from AstraZeneca, Merck Sharp & Dohme (MSD), Roche, Pfizer, GlaxoSmithKline (GSK) and Clovis Pharma; and research funding from Roche, MSD, AstraZeneca and Pfizer. Amit Oza: Principal investigator of investigator-initiated studies with AstraZeneca; institutional grant funding from AstraZeneca; and steering committee member (non-compensated) for AstraZeneca, Clovis Oncology and GSK. Geoff Hall: Research funding from IQVIA. Beatriz Pardo: Research funding from AstraZeneca, GSK, Clovis and MSD. Radoslaw Madry: Advisory board participation for AstraZeneca, Roche and GSK; and personal fees from AstraZeneca, Roche and GSK. David Cibula: Advisory board participation for AstraZeneca, Roche, Genmab, SOTIO, Merck and GSK. Jaroslav Klat: Reports no disclosures. Ana Montes: Reports no disclosures. Rosalind Glasspool: Principal investigator for trials sponsored by AstraZeneca, Clovis, Tesaro, Immunogen, Pfizer and Lilly; research funding from Clovis, Boehringer Ingelheim and Lilly/Ignyta; institution research funding from Tesaro; institutional fees from Novartis and personal fees from AstraZeneca, MSD, Clovis, Tesaro, GSK, Immunogen and SOTIO. Nicoletta Colombo: Personal fees from AstraZeneca, MSD, Roche, Tesaro, GSK, Clovis Oncology, PharmaMar, Pfizer, Amgen, Novartis, BIODCAD and Immunogen. Imre Pete: Reports no disclosures. Ana Herrero Ibáñez: Consulting/advisory board participation for GSK; speakers’ bureau participation for Clovis, GSK, MSD and PharmaMar; and research funding from AstraZeneca and Roche. Margarita Romeo Marín: Institution research funding from AstraZeneca, GSK, Clovis and Pfizer. Personal fees from MSD and GSK. Rumya Ilieva: Reports no disclosures. Constanta Timcheva: Principal investigator of clinical trials of AstraZeneca, Roche, Novartis, Pfizer and Merck; and member of advisory boards of Astellas, Servier and Novartis. Massimo Di Maio: Principal investigator of clinical trials of Roche, Merck, BeiGene, Novartis, Pfizer and Exelixis; member of advisory boards of AstraZeneca, Roche, Novartis, Pfizer, Eisai, Astellas, Janssen, Merck and Amgen; institutional research funding from Tesaro – GlaxoSmithKline. Christopher Blakeley: AstraZeneca employment and stock ownership. Rosie Taylor: AstraZeneca contractor. Alan Barnicle: AstraZeneca employment and stock ownership. Andrew Clamp: Research funding from AstraZeneca; and honoraria from AstraZeneca, Clovis Oncology, GSK/Tesaro and Eisai.

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