As reported in The Lancet Oncology by Susan M. Domchek, MD, and colleagues, the combination of olaparib and durvalumab showed activity in a cohort of patients with germline BRCA-mutated, HER2-negative metastatic breast cancer enrolled in a phase I/II basket study (MEDIOLA).

Susan M. Domchek, MD

Study Details

In the international study, 34 patients enrolled between June 2016 and May 2017 received olaparib at 300 mg twice daily for 4 weeks, and then a combination of olaparib at 300 mg twice daily and durvalumab at 1.5 g via intravenous infusion every 4 weeks until disease progression or unacceptable toxicity. Patients could not have received more than two previous lines of chemotherapy for metastatic breast cancer. The primary endpoints were safety/tolerability and 12-week disease control rate.

Toxicity

Grade ≥ 3 adverse events occurred in 11 patients (32%), with the most common being anemia (12%), neutropenia (9%), and pancreatitis (6%). A total of six serious adverse events occurred in four patients (12%) and consisted of anemia, hemolysis, hypercalcemia, dyspnea, pancreatitis, and hydronephrosis. Olaparib dose reductions due to adverse events occurred in six patients (18%). Adverse events led to treatment discontinuation in three patients, with causes consisting of anemia, arthralgia, and dyspnea. No treatment-related deaths were reported.

Responses

At 12 weeks, disease control was achieved in 24 (80.0%) of 30 evaluable patients. Objective response was observed in 19 patients (63.3%), including complete response in 1, and stable disease ≥ 11 weeks was observed in an additional 5 patients (17%). The disease control rate at week 28 was 50.0%.

Median duration of response was 9.2 months. At a median follow-up of 6.7 months, median progression-free survival was 8.2 months. At a median follow-up of 19.8 months, median overall survival was 21.5 months.

The investigators concluded, “[The] combination of olaparib and durvalumab showed promising antitumor activity and safety similar to that previously observed in olaparib and durvalumab monotherapy studies. Further research in a randomized setting is needed to determine predictors of therapeutic benefit and whether addition of durvalumab improves long-term clinical outcomes compared with olaparib monotherapy.”

Dr. Domchek, of the Basser Center for BRCA, University of Pennsylvania, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit thelancet.com.