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Activity of Olaparib and Durvalumab in Germline BRCA-Mutated Metastatic Breast Cancer


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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

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.

KEY POINTS

  • The disease control rate at week 12 was 80.0%.
  • Objective response was observed in 63.3% of patients.

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.


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