Olaparib Rechallenge Offers PFS Improvements in Ovarian Cancer

Ovarian cancer in woman: © blueringmedia - stock.adobe.com

Rechallenging patients with relapsed ovarian cancer who had previously received a poly-ADP ribose polymerase inhibitor (PARPi) with maintenance olaparib (Lynparza) demonstrated an improvement in progression-free survival (PFS), regardless of BRCA mutation status, according to results from the phase 3b OReO/ENGOT-ov38 study (NCT03106987).¹

Findings published in the Annals of Oncology showed that in patients with a BRCA mutation, the median PFS was 4.3 months with olaparib vs 2.8 months with placebo (HR, 0.57; 95% CI, 0.37-0.87, P =.022), and the 1-year PFS rates were 19% vs 0%, respectively. Among patients without a BRCA mutation, the median PFS was 5.3 months with olaparib vs 2.8 months with placebo (HR, 0.43; 95% CI, 0.26-0.71; P =.0023), and the 1-year PFS rates were 14% vs 0%.

“OReO/ENGOT-ov38 is the first randomized placebo-controlled trial to report data for rechallenge with a PARPi in patients with [platinum-sensitive relapsed ovarian cancer]. In meeting its primary endpoint, OReO demonstrated that rechallenge with maintenance olaparib provided a statistically significant, albeit modest, improvement in PFS compared with placebo in both the BRCA [mutated- and non-BRCA-[mutated] cohorts,” study authors wrote.

Study Design and Patient Characteristics

PFS was the primary end point of the study, and secondary end points included time to first subsequent therapy or death, time to second subsequent therapy or death, overall survival, health-related quality-of-life, safety, and tolerability.

Between June 2017 and February 2021, a total of 220 patients were evaluated in OReO/ENGOT-ov38. In the BRCA-mutated cohort, 74 patients were treated with olaparib and 38 were treated with placebo, while 72 received olaparib and 36 received placebo in the non-BRCA-mutated cohort. Among both cohorts, more than 85% of patients had received 3 or more lines of chemotherapy.

In the BRCA-mutated group, the median follow-up was 4.1 months (IQR, 2.7-8.5) with olaparib vs 2.8 months with placebo (IQR, 2.7-5.5), while median follow-up in the non-BRCA-mutated group was 2.9 months (IQR, 2.6-5.5) with olaparib vs 2.8 months (IQR, 2.6-2.9) with placebo.

Median treatment duration was 4.73 months (IQR, 2.8-9.5) with olaparib vs 3.35 months (IQR, 2.8-5.6) with placebo in the BRCA-mutated cohort and 3.98 months (IQR, 2.8-6.1) with olaparib and 2.86 months (IQR, 2.8-4.1) with placebo in the non-BRCA-mutated cohort.

Safety and Tolerability

Regarding safety, the most reported AEs among those receiving the olaparib rechallenge were fatigue/asthenia, nausea, and anemia. Most AEs were grade 1 to 2. Five patients (7%) in the BRCA-mutated olaparib group reported serious AEs, and 1 patient reported serious treatment-related AEs of anemia and neutropenia. No serious or treatment-related AEs were reported in the BRCA-mutated placebo group.

Serious AEs were reported in 11 patients (15%) in the non-BRCA-mutated olaparib group vs 2 patients (6%) in the placebo group. Three of the patients in the olaparib group reported serious treatment-related AEs of anemia, neutropenia, and general physical health deterioration.

No new safety signals were identified with the maintenance olaparib rechallenge; the safety profile was consistent with previous reports.

While the intention of the study was not to compare the BRCA-mutated vs non-BRCA-mutated subgroups, the differences in response were noteworthy.

“Although the study was not designed to compare these subgroups, as comparisons may be confounded by differences in the patient populations…and by limitations due to a small subgroup size, this observation is intriguing and warrants further investigation in future clinical trials,” authors wrote.

REFERENCE:

1. Pujade-Lauraine E, Selle F, Scambia G, et al. Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OreO/ENGOT-ov38): a phase IIIb trial. Ann Oncol. 2023;34(12):1152-1164. doi:10.1016/j.annonc.2023.09.3110