Niraparib Plus Pembrolizumab in Advanced Triple-Negative Breast Cancer


Key Points

  • Response was observed in 21% of evaluable patients.
  • Response rates were higher in patients with a BRCA mutation or PD-L1–positive disease.

In the phase II TOPACIO/KEYNOTE-162 trial reported in JAMA Oncology, Vinayak et al found evidence of activity of combined niraparib and pembrolizumab in a cohort of patients with advanced or metastatic triple-negative breast cancer, with higher response rates seen in patients with BRCA mutations or programmed cell death ligand 1 (PD-L1)-positive tumors.

Study Details

The study involved 47 evaluable patients from multiple U.S. sites. Patients were enrolled—irrespective of BRCA mutation status or PD-L1 expression status—between January and October 2017. Patients were given niraparib 200 mg once daily in combination with pembrolizumab 200 mg on day 1 of each 21-day cycle. Patients had received a median of one prior line of therapy in the metastatic setting.

Response Rates

Among the 47 evaluable patients, objective response was observed in 10 (21%), including complete response in 5 patients. An additional 13 patients had stable disease, yielding a disease control rate of 49%. Median duration of response was not reached at data cutoff; duration of response ranged from 4.6 to 15.9 months, with seven responders still receiving treatment at data cutoff. Median progression-free survival was 2.3 months.

Among 15 evaluable patients with BRCA mutations, objective response was observed in 7 (47%), the disease control rate was 80%, and median progression-free survival was 8.3 months. Among 27 evaluable patients with BRCA wild-type tumors, response was observed in 3 (11%), the disease control rate was 33%, and median progression-free survival was 2.1 months. Among 28 evaluable patients with PD-L1–positive disease, response was observed in 9 (32%) and the disease control rate was 50%; among 13 with PD-L1–negative disease, response was observed in 1 (8%) and the disease control rate was 46%.

Adverse Events

The most common treatment-related adverse events of grade ≥ 3 were anemia (18%), thrombocytopenia (15%), and fatigue (7%). Immune-related adverse events were reported in eight patients (15%), with the most common being hypothyroidism (7%); grade 3 events occurred in two patients (4%), consisting of adrenal insufficiency and polymyalgia rheumatica.

The investigators concluded, “Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic [triple-negative breast cancer], with numerically higher response rates in those with tumor BRCA mutations. The combination therapy was safe with a tolerable safety profile, warranting further investigation.”

Shaveta Vinayak, MD, of Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle Cancer Care Alliance, is the corresponding author for the JAMA Oncology article.

Disclosure: This study was supported by TESARO: A GSK Company, and Merck & Co. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.