Promising activity of maintenance olaparib in advanced breast cancer patients responding to platinum-based chemotherapy.

Tan TJ et al. has recently published the results of a phase II study (DORA) in Clinical Cancer Research. The study involved 45 advanced, triple-negative breast cancer (TNBC) patients who achieved at least disease control following first- or second-line platinum-based chemotherapy. Patients were randomized to receive olaparib or olaparib combined with durvalumab. The study's primary objective was to compare progression-free survival (PFS) versus a historical control of continued platinum-based therapy.

After 9.8 months of median follow-up, median PFS was 4.0 months with olaparib alone and 6.1 ?months with the combination. Both results were significantly longer than the historical control (P = 0.0023 and P < 0.0001, respectively). Clinical benefit rates (SD ≥24 weeks or CR/PR) were 44% ?and 36% in the monotherapy and combination arms, respectively. Moreover, clinical benefit was seen irrespective of germline BRCA mutation or PD-L1 status but seemed to be associated with objective responses to prior platinum, particularly in the olaparib-alone arm. Medan overall survival was 21.7 months (95%CI 7.7-NE) and 18.3 months (95%CI 8.2-NE) in olaparib and olaparib+durvalumab arms, respectively. No new safety signals were reported.

The DORA study provides two important data:

-????????? PARP inhibition may represent an interesting chemotherapy-free maintenance treatment in TNBC patients responding to platinum-based chemotherapy

-????????? combination of PARPi and checkpoint inhibitors is feasible and safe and may be considered a safe experimental option in BRCA1/2mut patients following neoadjuvant chemoimmunotherapy

https://doi.org/10.1158/1078-0432.CCR-23-2513