Early data from a phase Ib trial suggest that the immune checkpoint inhibitor pembrolizumab has modest activity against heavily pretreated metastatic triple-negative breast cancer (mTNBC).
Among 27 women with advanced triple-negative breast cancer (tumors lacking HER2, estrogen, and progesterone receptors) enrolled in a basket trial for cancers expressing the programmed death-1 ligand (PD-L1), the overall response rate to biweekly pembrolizumab (Keytruda) was 18.5%, reported Dr. Rita Nanda of the University of Chicago and colleagues (J Clin Oncol. 2016 May 2. doi: 10.1200/JCO.2015.64.8931).
Dr. Rita Nanda
“Overall, these results support further development of pembrolizumab for the treatment of mTNBC,” they said.
The TNBC study was included in the open-label, multicohort Keynote 012 study looking at the use of pembrolizumab in patients with advanced solid tumors expressing PD-L1.
The investigators evaluated PD-L1 status in 111 women with mTNBC, and identified 65 with tumors expressing the target, 32 of whom were enrolled in the trial.
The patients were treated with pembrolizumab 10 mg/kg intravenously every 2 weeks until unacceptable toxicity or disease progression, or at the discretion of the investigator. Clinically stable patients with first radiologic evidence of disease progression according to Response Evaluation Criteria for Solid Tumors (RECIST) could be continued on the checkpoint inhibitor until evidence of progression could be shown on a second scan 4 or more weeks later.
The patients received a median of five doses (range, 1-36). After a median follow-up of 10 months, the overall response rate among 27 patients evaluable for response was 18.5%, consisting of one complete response, four partial responses, and seven cases of stable disease. Thirteen patients had disease progression on pembrolizumab, and two patients discontinued therapy before the first scan.
The median time to response was 17.9 weeks; the median duration of response had not been reached by the time of data cut-off on March 25, 2015.
The adverse event profile was similar to that seen with pembrolizumab in the other study cohorts (gastric, urothelial, and head and neck cancers), with generally mild arthralgia, fatigue, myalgia, and nausea. However, there were five grade 3 or greater toxicities, including anemia, aseptic meningitis, lymphopenia, headache, and pyrexia, and one patient died from treatment-related disseminated intravascular coagulation accompanied by a grade 4 decrease in blood fibrinogen.
The investigators noted that the overall response rate seen in the TNBC cohort “makes it the first published report showing clinical activity for an immune checkpoint inhibitor in a heavily pretreated mTNBC population.”
Overall response rates for the other cohorts in the study were 21.4% for patients with head and neck cancers, 22.2% for those with gastric cancers, and 27.6% for those with urothelial cancers.
The study was sponsored by Merck & Co. Dr. Nanda and several coauthors disclosed consulting, research funding, and/or honoraria from the company, and four of the 12 coauthors are employees.