For the first time, immunotherapy added to chemotherapy has improved overall survival in metastatic triple-negative breast cancer, as demonstrated by the Keynote-355 study, led by Dr. Javier Cortés, founder and director of the International Breast Cancer Center (IBCC), and with Dr. José Manuel Pérez, deputy director of the IBCC, also participating. The study is being presented at the ESMO Congress 2021, the leading oncology congress in Europe, which every year brings together oncologists and professionals from all over the world.
Metastatic triple-negative breast cancer represents around 15% of all diagnosed cases of breast cancer; it is characterized by its high aggressiveness and by having the worst prognosis, with few available therapeutic options to combat efficiently. Until now, immunotherapy, which is one of the most important avenues of clinical research against these tumours, has shown that it can improve their prognosis.
“At the ESMO Congress 2021 we are presenting the Keynote-355 study which not only demonstrates that immunotherapy improves the prognosis of breast cancer patients, but also, for the first time, that immunotherapy improves the overall survival of breast cancer patients. We knew it from other pathologies: melanoma, lung cancer and others; but we had never been able to demonstrate it in breast cancer”, says Dr. Cortés.
The randomized, double-blind, phase III clinical trial, Keynote-355, tested one type of immunotherapy, pembrolizumab, a monoclonal antibody that targets the PD-1 receptor, found on the surface of lymphocytes, and acts by stimulating the immune system to destroy tumour cells.
This clinical trial was conducted in 209 centers in 29 countries, and included 847 patients with metastatic triple-negative breast cancer who had not received any prior treatment for metastatic disease. Patients were randomized (2:1) to receive treatment with either chemotherapy and pembrolizumab (566 patients) or chemotherapy and placebo (281 patients). The primary endpoints of the study were progression-free survival and overall survival.
After a median follow-up of around 44 months, this study has confirmed that the addition of pembrolizumab to chemotherapy treatment statistically improves overall survival, the second primary endpoint of the study, significantly, with a 27% reduction in risk of death compared to chemotherapy and placebo treatment in patients whose tumours had PD-L1 protein expression with a CPS score of 10 or higher. In absolute terms, the addition of pembrolizumab increases the overall survival of these patients by almost seven months.
The results of Keynote-355 respond to a long line of research with pembrolizumab plus chemotherapy, led by the IBCC’s Dr. Cortés, which has previously resulted in the publication of other studies, including a paper in December 2020 in The Lancet, to study the impact of this treatment on progression-free survival. The study significantly demonstrated that the risk of progression or death was reduced by 35%, compared to chemotherapy and placebo, in patients whose tumours had PD-L1 protein expression with a CPS score of 10 or higher.
These results led to accelerated approval by the American drug agency (FDA), in November 2020, of the combination of chemotherapy and pembrolizumab for the treatment of this subgroup of patients.
The new results from this study have now positioned the combination of pembrolizumab and chemotherapy as the first-line treatment of choice for patients with metastatic triple-negative breast cancer.