236O - Olaparib (ola) plus bevacizumab (bev) as maintenance (mx) therapy in patients (pts) with newly diagnosed advanced ovarian carcinoma (OC): Japan subset of the PAOLA-1 trial

Background

International Phase III PAOLA-1/ENGOT-ov25 trial (NCT02477644) found that pts with newly diagnosed advanced OC who received mx ola in addition to standard first-line platinum-based chemotherapy (PBC) plus bev had a statistically significant progression-free survival (PFS) benefit (HR 0.59; 95% CI 0.49–0.72; Ray-Coquard et al. NEJM 2019). Here we present results of the Japan subset.

Methods

Pts had newly diagnosed, FIGO stage III–IV, high-grade OC, fallopian tube or primary peritoneal cancer and were in clinical complete or partial response following PBC + bev. Pts were randomised (2:1) to ola tablets (300 mg bid for up to 24 months [m]) + bev (15 mg/kg d1, q3w for up to 15 m in total) or placebo (pbo) + bev, stratified by treatment outcome and tumour BRCA mutation (tBRCAm) status. Primary endpoint was investigator-assessed PFS (modified RECIST v1.1).

Results

24 pts were randomised, 15 to ola + bev and 9 to pbo + bev. Pt characteristics, including tBRCAm and homologous recombination deficiency (HRD) status were generally well balanced; 20% vs 22% of pts had a tBRCAm in the ola + bev vs pbo + bev arms and 67% had an HRD positive test result in each arm. Median follow up was 27.7 m in the ola + bev arm vs 24.0 m in the pbo + bev arm. Median PFS was 27.4 m (11.1–not reached) in the ola + bev arm vs 19.4 m (3.1–24.0) in the pbo + bev arm (Table).

Grade ≥3 adverse events (AEs) were reported by 73% vs 33% of pts in the ola + bev and the pbo + bev arms, respectively; the most common were anaemia (n=5 vs n=0) and leukopenia (n=4 vs n=0). AEs led pts to dose interruptions (73% vs 44%), reductions (60% vs 0%) and discontinuations (27% vs 11%) in the ola + bev vs the pbo + bev arms, respectively.

Conclusions

In the Japan subset of PAOLA-1, the efficacy results were generally consistent with the overall efficacy results, and the proportion of pts who had a grade ≥3 AE was generally higher than in the overall population. A limitation of this subgroup analysis is the small number of pts.

Clinical trial identification

NCT02477644

Editorial acknowledgement

Medical writing assistance was provided by Laura Smart, MChem, of Mudskipper Business Limited