Episode 24: Olaparib as a treatment option in germline BRCA-mutated, HER2- metastatic breast cancer: the OlympiAD trial

In this episode of WND focusing on breast cancer, Dr. Kevin Punie from GZA Hospitals and Prof. Evandro de Azambuja from Institut Jules Bordet will delve into two publications from the OlympiAD trial. This phase 3 trial assessed patients with germline BRCA-mutated, HER2- metastatic breast cancer who had received ≤2 prior lines of chemotherapy. The trial compared treatment with the PARP inhibitor olaparib to the treatment chosen by physicians.

Previous data indicated improved PFS, and now, with an additional 23 months of follow-up, OS data are presented. While OS was numerically higher for patients treated with olaparib, the difference was not statistically significant. However, patients receiving olaparib had a longer treatment duration compared to chemotherapy (median 8.4 vs. 4 months). Notably, patients treated with olaparib as a first-line therapy showed a substantial OS benefit (22 vs. 13 months).

Statistically significant benefits favouring olaparib over chemotherapy were observed in PFS. Subgroup analyses, including hormone receptor status, germline BRCA mutations, visceral vs. non-visceral metastases, prior chemotherapy, prior platinum-based chemotherapy, and progressive disease at randomization, all indicate benefits from olaparib treatment. No new toxicities were reported, and patients experienced an improved QoL on olaparib.

While ESMO guidelines emphasize the importance of germline BRCA status as a pivotal biomarker for patients with advanced HER2- breast cancer, this test is not typically requested until second-line therapy. Initial therapy involves endocrine therapy and CDK4/6 inhibitors, with germline status testing occurring upon progression to second-line treatment, primarily focusing on BRCA1/2 mutations.

Survival benefits were statistically significant only among patients who received PARP inhibitors as first-line treatment. This suggests a potential overlapping indication for triple-negative patients in the first line. However, experts lean towards checkpoint inhibition with chemotherapy as the first choice in PD-L1 positive patients, reserving PARP inhibition for later lines of treatment.