Pembrolizumab Monotherapy for Heavily Pretreated Patients With Metastatic Breast Cancer and High Tumor Mutational Burden

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Findings from the ASCO-designed phase II Targeted Agent and Profiling Utilization Registry (TAPUR) basket trial, reported in the Journal of Clinical Oncology by Alva et al, indicated that pembrolizumab showed activity in heavily pretreated patients with metastatic breast cancer and high mutational burden.

Study Details

The U.S. multicenter study enrolled 28 women with metastatic disease and tumor mutational burden ranging from 9 to 37 mutations/megabase between October 2016 and July 2018. Overall, 26 (93%) had received three or more prior systemic therapies (two had received two prior therapies) and 23 (82%) had received prior radiotherapy. Among 19 patients with known microsatellite instability (MSI) status, 18 had MSI-stable disease. A total of 25 (89%) had HER2-negative tumors, 14 (50%) had hormone receptor–positive disease, and 13 (46%) had triple-negative disease. Data on PD-L1 expression were not collected. Patients received pembrolizumab at either 2 mg/kg (n = 8) or 200 mg (n = 20) every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was rate of disease control, defined as objective response or stable disease for 16 weeks or longer.

Disease Control


  • Disease control was observed in 37% of patients and objective response was observed in 21%.
  • Median overall survival was 30.6 weeks.

Disease control was observed in 10 patients (37%, 95% confidence interval = 21%–50%) and objective response was observed in 6 (21%, 95% CI = 8%–41%). Median progression-free survival was 10.6 weeks (95% CI = 7.7–21.1 weeks); median overall survival was 30.6 weeks (95% CI = 18.3–103.3 weeks). There was no apparent relationship between tumor mutational burden and progression-free or overall survival.

Adverse Events

Drug-related grade 3 to 4 adverse events occurred in three patients (11%) and drug-related serious adverse events were reported in three patients (11%). Grade 3 drug-related adverse events consisted of pulmonary embolism, weight loss, hypoalbuminemia, and hyponatremia. Grade 2 or 3 drug-related serious adverse events consisted of colonic obstruction, diarrhea, urinary tract infection, and hepatic failure.

The investigators concluded, “Pembrolizumab monotherapy has antitumor activity in heavily pretreated patients with metastatic breast cancer characterized by high tumor mutational burden. Our findings support the recent U.S. Food and Drug Administration approval of pembrolizumab for treatment of patients with unresectable or metastatic solid tumors with high tumor mutational burden without alternative treatment options.”

Pam K. Mangat, MS, of ASCO, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. Pembrolizumab was provided by Merck Sharp & Dohme Corp, with additional funding provided by AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly, Genentech, and Pfizer. 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®.