Immunotherapy drug shows efficacy against metastatic triple negative breast cancer

Pembrolizumab has been found to be effective for metastatic triple negative breast cancer (mTNBC), according to an international clinical trial led by NYU Langone’s Perlmutter Cancer Center. The immunotherapy drug is already approved by the FDA for other forms of cancer.

This trial involved two cohorts:

• Cohort A: 170 patients with heavily pretreated mTNBC, regardless of the expression of a protein called programmed death receptor ligand 1 (PD-L1)
• Cohort B: 52 patients with PD-L1-positive tumors who received pembrolizumab as a first-line therapy.

Sylvia Adams, MD, Associate Professor of Medical Oncology at Perlmutter Cancer Center and principal investigator of this study, presented the findings at the annual meeting of the American Society of Clinical Oncology in Chicago. This multisite trial was conducted at 17 medical centers across 4 continents.

Results showed that pembrolizumab shrank tumors in cohort A by more than 30% in 8 of 170 patients (5%). It stabilized disease in 35 of those patients (21%). Of the 8 patients who had tumor reduction, all had lived at least another year. The remaining patients in cohort A had a lower chance of survival.

In cohort B, 12 of 52 patients (23%) saw tumors shrink by more than 30%, while disease was stabilized in 9 of the patients (17%).

Dr. Adams noted that cohort A is the first phase 2 study of an immunotherapy for triple negative breast cancer to be reported. It represents the largest cohort of patients with mTNBC that have been treated with immunotherapy to date.

“Our results suggest that this treatment as a single agent is effective for mTNBC,” she explained. “Interestingly, we found that activity of pembrolizumab was seen in both PD-L1-positive and negative tumors. These data are very encouraging, especially for a disease that is extremely aggressive and has limited treatment options when it metastasizes.”

The goals of cohort B, for which survival data are not yet complete, were primarily to prove pembrolizumab’s safety and, secondarily, to explore its efficacy as a first-line treatment. Both goals appear to have been met.

“This research contributes to a larger body of knowledge that could help provide better outcomes to women with few treatment options,” Dr. Adams added. “The data also suggest that immunotherapy administered earlier in the disease course is more beneficial, as response rates are much greater in first- compared to second- or later lines of therapy.”

Pembrolizumab is marketed under the name Keytruda. According to the study results, it was well tolerated by both cohorts at a 200 mg dose every 3 weeks. Only 12% of patients in cohort A and 8% in cohort B experienced severe side effects. The most common side effects in both cohorts were fatigue and nausea. Although side effects led to discontinuation of treatment in 7 patients from cohort A, no patients in cohort B discontinued treatment due to adverse side effects.

Dr. Adams says more research is needed, including identification of biomarkers, testing of combination therapies, and expanding clinical studies to larger patient cohorts. Still, she is optimistic.

“Although only a small subset of women responded to the drug, within that subset pembrolizumab worked extremely well and responses were durable,” she said. “By causing fewer side effects and promoting longer life expectancy, pembrolizumab could help change the outcome of mTNBC.”

Merck, the manufacturer of pembrolizumab, funded this clinical trial and provided Dr. Adams and her colleagues with research support.

To read more about this study, click here.