Pembrolizumab demonstrated antitumor activity against metastatic breast cancer with high tumor mutational burden (hTMB), according to an analysis of the TAPUR study published in the Journal of Clinical Oncology.

“Our findings support the recent US Food and Drug Administration approval of pembrolizumab for treatment of patients with unresectable or metastatic solid tumors with hTMB without alternative treatment options,” the authors wrote.

The phase 2 TAPUR study ( Identifier: NCT02693535) is a basket trial evaluating the antitumor activity of targeted agents in different cancer types with potentially actionable mutations. The present analysis included a cohort of 28 patients with metastatic breast cancer with hTMB defined as 9 to 37 mutations per megabase, who were treated with pembrolizumab. The primary endpoint was disease control defined as objective response or stable disease. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).

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At baseline, the median age of the study cohort was 63 years (range, 36-78). The majority (93%) of the patients had at least 3 prior lines of treatment, and 82% had prior radiation therapy. There were 46% of patients with triple-negative disease, 43% with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative disease, 7% with HR-positive and HER2-positive disease, and 4% with HR-negative and HER2-positive disease. Microsatellite instability was high among 4% of the patients; 64% had stable microsatellite instability, and 32% were not reported.

Pembrolizumab demonstrated antitumor activity, with a disease control rate of 37% and an objective response rate of 21%. The median PFS was 10.6 weeks and median OS was 30.6 weeks; neither of which was associated with hTMB. Treatment-related grade 3-4 adverse events occurred in 11% of the patients, and 11% developed serious adverse events. There were 6 patients who discontinued treatment due to an adverse event.

The authors concluded that “…the results from this TAPUR Study cohort indicate that single-agent pembrolizumab has meaningful clinical activity in heavily pretreated patients with [metastatic breast cancer] for [high] TMB, including patients with both HR-positive and triple-negative breast cancer.”

Disclosure: This clinical trial is supported by several pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.


Alva AS, Mangat PK, Garrett-Mayer E, et al. Pembrolizumab in patients with metastatic breast cancer with high tumor mutational burden: results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study. J Clin Oncol. Published online April 12, 2021. doi:10.1200/JCO.20.02923