Progression-Free Survival Benefit from Maintenance Olaparib in Patients with Platinum-Sensitive Relapsed Ovarian Cancer by BRCA and Other Homologous Recombination Repair Gene Mutation Status (ORZORA Trial)

2021 Year in Review - Ovarian Cancer —March 21, 2022

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Ovarian Cancer

Results of the ORZORA trial indicate that patients with platinum-sensitive relapsed ovarian cancer derived progression-free survival benefit from maintenance olaparib, irrespective of somatic or germline BRCA mutation status.

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 with a BRCA mutation (BRCAm). The results of this trial were reported at the 2021 Society of Gynecologic Oncology Annual Meeting.

This trial enrolled patients with platinum-sensitive relapsed ovarian cancer harboring a germline BRCAm (gBRCAm) or somatic (sBRCAm), who were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment. Eligible patients received maintenance olaparib (400 mg twice a day) until disease progression. Co-primary end points were investigator-assessed progression-free survival (PFS) in the BRCAm and sBRCAm cohorts (conducted at 60% maturity). Secondary end points included time to second progression or death (PFS2), health-related quality of life (HRQOL) as assessed using the Functional Assessment of Cancer Therapy–Ovarian Cancer outcome index, and tolerability. Tumor BRCAm status was assessed by central screening using the Myriad myChoice CDx assay; somatic or germline BRCAm status was determined by central genomic testing using the Myriad BRACAnalysis CDx assay. An additional exploratory cohort comprised patients with predefined homologous recombination repair gene mutations (HRRm) excluding BRCAm (determined using the FoundationOne CDx assay). The data cutoff date was April 17, 2020.

Of the 181 patients enrolled, 145 patients had BRCAm, 55 patients had sBRCAm, 87 patients had gBRCAm, and 33 patients had HRRm. Patient characteristics were similar between the somatic and germline BRCAm cohorts in terms of ≥3 previous lines of chemotherapy (38% vs 48%, respectively); partial response to previous platinum therapy (45% vs 49%, respectively); and the presence of a tumor BRCA1 mutation (65% vs 64%, respectively).

At a median follow-up of 22.3 months, median PFS was similar in the BRCAm (18.0 months), sBRCAm (16.6 months), gBRCAm (19.3 months), and HRRm cohorts (16.4 months). Median PFS2 was 30.9 months for the BRCAm cohort; 24.7 months for the sBRCAm cohort; and 32.5 months for the gBRCAm cohort. HRQOL was comparable in the BRCAm and sBRCAm cohorts.

In the safety population (n = 177), the most frequent adverse events (AEs) were nausea (54%), fatigue (43%), anemia (42%), and vomiting (28%). Serious AEs occurred in 25% of patients; grade ≥3 AEs occurred in 35% of patients. Treatment discontinuation as a result of AEs was reported in 5% of patients. Two new primary malignancies were reported, both of which were acute myeloid leukemia; no cases of myelodysplastic syndrome occurred.

Based on these results, patients with platinum-sensitive relapsed ovarian cancer derive PFS benefit from maintenance olaparib, irrespective of somatic or germline BRCAm status.

Source: Pignata S, Oza A, Hall G, et al. ORZORA: maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer: outcomes by somatic and germline BRCA and other homologous recombination repair gene mutation status. Gynecol Oncol. 2021;162(suppl_1):S29.

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Last modified: April 7, 2022

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