Maintenance Olaparib Rechallenge in Platinum-Sensitive Relapsed Ovarian Cancer

1. Median PFS was improved in the olaparib arm vs placebo, with an HR 0.57 in the BRCAm cohort and HR 0.43 in the non-BRCAm cohort.

2. Treatment-related serious adverse events were reported in 1-4% in the olaparib arm (with anemia, neutropenia, and general physical health deterioration).

Evidence Rating Level: 1 (Excellent)

Study Rundown: Maintenance therapy with poly(ADP-ribose) polymerase inhibitors (PARPi) is a standard treatment for ovarian cancer, both in patients with platinum-sensitive relapsed disease and newly diagnosed cases, especially those with BRCA mutations (BRCAm) or homologous recombination deficiency (HRD). However, it’s uncertain if patients will benefit from rechallenge with PARPi maintenance therapy upon relapse. This study investigated whether rechallenging with maintenance olaparib is beneficial for patients with platinum-sensitive relapsed ovarian cancer who previously received a PARPi. The primary endpoint was progression-free survival (PFS) and secondary endpoints included time from randomization to first subsequent therapy or death (TFST), time from randomization to second subsequent therapy or death (TSST), overall survival (OS), quality of life (QoL), and safety. In the BRCAm cohort, the median PFS was 4.3 months for olaparib vs 2.8 months for placebo, HR 0.57. In the non-BRCAm cohort, the median PFS was 5.3 months for olaparib vs 2.8 months for placebo, with an HR 0.43. Subgroup analysis of HRD positive and negative non-BCRAm patients found similar PFS results but it was not statistically significant. Median TFST with olaparib versus placebo in the BRCAm cohort was 5.8 vs 5.1 months, HR 0.56, and in the non-BRCAm cohort was 7.9 vs 4.3 months, HR 0.39. Median TSST showed improvement with olaparib versus placebo in both cohorts but results were not statistically significant. Median OS in the BRCAm cohort was 20.1 months with olaparib and 20.9 months with placebo, with HR 0.88 (not statistically significant), and OS data was immature in the non-BRCAm cohort. QoL was not statistically significant between both arms in both cohorts. Treatment-related serious adverse events were reported in 1% of the olaparib group for the BRCAm cohort and 4% of patients in the olaparib group for the non-BRCAm cohort. The strengths of this study included the robust methodology and the limitations of this study included differences in pre-treatment among patients and immature OS data. Overall rechallenging with maintenance Olaparib resulted in some improved outcome measures compared to a placebo, regardless of whether the patients had BRCA mutations or not.

Click to read the study in Ann. Oncol

Relevant Reading: Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial

In-Depth [randomized controlled trial]: This double-blind, placebo-controlled, multicenter phase IIIb trial enrolled patients (with relapsed ovarian cancer, peritoneal cancer, and/or fallopian tube cancer who failed recent platinum-based chemotherapy and previously received maintenance PARPi) into two cohorts; BRCAm and non-BRCAm and randomized them (2:1) to olaparib (74 patients in the BRCAm cohort, 72 in the non- BRCAm cohort) or placebo (38 in BRCAm cohort, 36 in non- BRCAm cohort). In the BRCAm cohort, median PFS was 4.3 months for olaparib vs 2.8 months for placebo, with an HR 0.57 (95%CI, 0.37-0.87, p=0.0220), and 1-year PFS rates were 19% vs 0%, respectively. In the non-BRCAm cohort, the median PFS was 5.3 months for olaparib vs 2.8 months for placebo, with an HR 0.43 (95%CI, 0.26-0.71, p=0.0023), and 1-year PFS rates were 14% versus 0%, respectively. Subgroup analysis of HRD positive and negative non-BCRAm patients found similar PFS results but it was not statistically significant. Median TFST with olaparib versus placebo in the BRCAm cohort was 5.8 vs 5.1 months, HR 0.56 (95%CI, 0.36-0.88, p=0.0117), and in the non-BRCAm cohort was 7.9 vs 4.3 months, HR 0.39 (95%CI, 0.23-0.65, p=0.0011). Median TSST showed improvement with olaparib versus placebo in both cohorts but results were not statistically significant. Median OS in the BRCAm cohort was 20.1 months with olaparib and 20.9 months with placebo, with HR 0.88 (95%CI, 0.52-1.53, p=0.44), and OS data was immature in the non-BRCAm cohort. QoL was not statistically significant between both arms in both cohorts. Treatment-related serious adverse events were reported in 1% in the olaparib group (anemia and neutropenia) for the BRCAm cohort and 4% patients in the olaparib group (anemia, neutropenia, general physical health deterioration) for the non-BRCAm cohort. Overall rechallenging with maintenance olaparib resulted in some improved outcome measures compared to a placebo, regardless of whether the patients had BRCA mutations or not.

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