PARP inhibitor rechallenge improves PFS in ovarian cancer

Results from the phase 3 OReO/ENGOT Ov-38 trial demonstrated that rechallenge with maintenance olaparib significantly prolonged progression-free survival (PFS) compared with placebo in both BRCA1/2-mutated and non-BRCA1/2-mutated disease.

Although most patients achieve a long-term response, most ultimately progress on PARP inhibitor maintenance therapy. The randomised, double-blind, phase 3 OReO/ENGOT Ov-38 study (NCT03106987) evaluated PARP inhibitor maintenance re-treatment in this setting. Dr Eric Pujade-Lauraine (Université Paris Descartes, France) presented the results [1].

A total of 112 patients were BRCA1/2 mutated (BRCAm) and 108 patients were non-BRCA mutated (non-BRCAm). Patients were heavily pre-treated, with 93% (BRCAm) and 86% (non-BRCAm) receiving ≥3 prior lines of any chemotherapy. In the BRCAm cohort, >90% of patients had olaparib as first PARP inhibitor; in the non-BRCAm cohort, >50% of patients had niraparib as first PARP inhibitor. Both cohorts randomised patients 2:1 to olaparib tablets (300 mg twice daily) or placebo until progression. Primary endpoint was investigator-assessed PFS.

In the BRCAm cohort, median PFS was 4.3 months for olaparib versus 2.8 months for placebo (HR 0.57; P=0.022). PFS rates were 35% versus 13% at 6 months and 19% versus 0% at 12 months. In the non-BRCAm cohort, median PFS was 5.3 months for olaparib versus 2.8 months for placebo (HR 0.43; P=0.002). PFS rates in the non-BRCAm cohort were 30% versus 7% at 6 months and 14% versus 0% at 12 months. In an exploratory analysis, benefit in the non-BRCAm cohort appeared consistent irrespectively of HRD status. No new safety signals were observed and discontinuations due to adverse events were low.

Based on these results, Dr Pujade-Lauraine concluded that “in a heavily pre-treated ovarian cancer population, rechallenge with maintenance following response to platinum-based chemotherapy provided a statistically significant improvement of PFS compared with placebo, irrespectively of BRCA-mutation status. A proportion of patients derived clinically relevant long-term benefit.”

1. Pujade-Lauraine E, et al. Maintenance olaparib rechallenge in patients (pts) with ovarian carcinoma (OC) previously treated with a PARP inhibitor (PARPi): Phase IIIb OReO/ENGOT Ov-38 trial. Abstract LBA33, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November, 202115 February, 2024