Pembrolizumab has been shown to be active on its own, but has not been shown to improve overall survival compared to standard chemotherapy treatment in patients with previously treated triple-negative metastatic breast cancer, according to the clinical study KEYNOTE-119, published in The Lancet Oncology. Dr. Javier Cortés, director of the International Breast Cancer Center (IBCC), is one of the world leaders of this international clinical trial.
Immunotherapy is one of the most important avenues of clinical research for patients with advanced triple-negative breast cancer. This subtype of breast cancer has the worst prognosis and accounts for around 15% of all diagnosed breast cancer cases.
Pembrolizumab is a monoclonal antibody directed against the PD-L1 receptor, found on the surface of lymphocytes, and works by stimulating the immune system to kill cancer cells.
The phase III clinical trial KEYNOTE-119 was conducted in 150 centres in 31 countries, and included 622 patients with triple-negative advanced breast cancer who had received one or two previous treatments for advanced disease. Patients were randomly assigned to the two arms of the study, with 312 receiving treatment with pembrolizumab and 310 with chemotherapy. The primary endpoint of the study was overall survival, which was analyzed in different groups of patients according to PD-L1 biomarker expression using the Combined Positive Score (CPS).
Treatment with pembrolizumab did not improve overall survival in patients whose tumours had PD-L1 expression based on CPS with a result of 10 or higher, nor in patients whose tumours had PD-L1 expression based on CPS with a result of 1 or higher, nor in the overall survival of patients involved in the study.
On an exploratory basis, an improvement in overall survival was observed in patients whose tumours had PD-L1 protein expression based on CPS with a result of 20 or higher. “Unfortunately, this was not the population chosen for the primary endpoint of the study,” explains Dr. Cortés.
However, the results of this clinical trial could help in the design of future clinical studies with pembrolizumab as the sole therapy in this group of patients, but specifically selecting those patients with PD-L1-enriched tumours.
Although this primary objective has not been achieved, it should be remembered that in the clinical trial, KEYNOTE-355, the addition of pembrolizumab to treatment with first-line chemotherapy significantly reduced the risk of progression or death by 35% in patients with triple-negative metastatic breast cancer, compared with chemotherapy and placebo, in patients whose tumours had expression of the PD-L1 protein, using the CPS, with a result of 10 or higher.