The phase III OlympiAD clinical trial demonstrated a progression-free survival benefit for olaparib compared to physician’s choice of chemotherapy in patients with germline BRCA1 or BRCA 2 mutations who had human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. Whether olaparib also conferred overall survival benefit remained unclear.
A recent analysis of OlympiAD’s final results published in Annals of Oncology indicate that one group derived an overall survival benefit of nearly 50%—patients who had received prior chemotherapy for metastatic disease.
Breast cancer patient talking with doctor. Source: Getty
Researchers led by Mark Robson, MD, of Memorial Sloan Kettering Cancer Center in New York, reported the planned final overall survival results and common adverse events in January.
The trial enrolled 302 patients of whom 205 received olaparib and 97 received capacitabine, vinorelbine or eribulin, depending on physician’s choice.
With a median follow up of 25 to 26 months, median overall survival for patients receiving olaparib was 19.3 months, while those receiving physician’s choice of chemotherapy had overall survival of 17.1 months. While the overall difference indicated a reduction in mortality risk of 10%, it did not reach statistical significance.
A subgroup analysis found a notable variation in overall survival (OS) benefit, however. Patients who had received no prior chemotherapy for metastatic breast cancer saw a significant reduction in mortality risk of 49% (HR: 0.51, 95% CI 0.29-0.90).
Non-significant reduction in mortality was also seen in triple negative patients (HR 0.93, 0.62-1.43), hormone receptor positive patients (HR 0.86, 0.55-1.36) and patients with prior platinum treatment (HR 0.83, 0.49-1.45) and previous treatment, but not with platinum therapy (HR 0.91, 0.64-1.33). Olaparib did not improve overall survival at all for patients who had already had second- or third-line treatment (HR 1.13, 0.79-1.64).
Few patients discontinued treatment (4.9%) and extended olaparib therapy did not increase the risk of anemia.
The authors concluded that “while there was no statistically significant improvement in OS with olaparib compared to [therapy of physician’s choice], there was the possibility of meaningful OS benefit among patients who had not received chemotherapy for metastatic disease.