The addition of pembrolizumab to chemotherapy as a first line treatment appears to provide a progression-free survival benefit to patients diagnosed with triple-negative breast cancer when compared to chemotherapy alone, researchers reported at the ASCO 2020 virtual congress.

Patients whose tumours contained higher levels of PD-L1 – the target of  pembrolizumab — achieved  four months more of progression free survival than the standard-of-care treated patients, said Dr Javier Cortes, head of the breast cancer program at IOB Institute of Oncology in Madrid and Barcelona.

He reported that this group of patients achieved a median progression-free survival of 9.7 months compared with 5.6 months for patients who were only treated with the chemotherapy regimen (P=0.0012). That met a pre-specified boundary for statistical significance of P=0.00411.

In the KEYNOTE-355 study, patients with metastatic or relapsed triple negative breast cancer – a disease with few treatment options – were stratified by the level of PD-L1. The high level PD-L1 patients group had a combined positive score of 10 or greater, Dr Cortes explained in his oral presentation.

In the group of patients with a PD-L1 combined positive score of 1 or greater, the results were attenuated. The progression-free survival in this group was 7.6 months if people were treated with pembrolizumab and 5.6 months if they were just treated with chemotherapy (P=0.0014),  but that result fell outside of the pre-specified boundary for statistical significance of  P=0.00111.

The different stratification were the co-primary endpoints of the Keynote-355 study. Dr Cortes said there were no statistical differences between the groups of patients based on combined positive scores.

“Pembrolizumab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival as compared with chemotherapy alone for a first-line treatment of patients with metastatic triple-negative breast cancer with PD-L1 combined positive score of 10 or higher,” he said.

The results are an exciting development  for women with triple-negative breast cancer, said Dr Alice Police, regional director of breast care for Northwell Health Cancer Institute, Sleepy Hollow, New York.

“The great thing about pembrolizumab is that it is the first really targeted therapy for triple-negative breast cancer,” she said, in an AASCO discussion forum on the research. “This is an amazing and much needed development in the treatment of triple-negative breast cancer.”

However, Dr Police cautioned: “It is early days yet. We only have about a year and a half of follow-up. The long-term benefit remains to be seen. We have been able to get women with hormone-positive cancer to live a long time with their disease so we hope this will be another treatment that will do the same for women with  metastatic triple negative disease, turn it into a chronic disease.”

In the study, Dr Cortes and colleagues recruited 847 patients and randomly assigned 566 patients to receive pembrolizumab plus chemotherapy, while 281 patients were assigned to chemotherapy plus placebo. Overall, 843 of the patients began therapy, and 777 discontinued over the course of the treatment, mainly due to disease progression.

In KEYNOTE-355, patients with previously untreated metastatic triple-negative breast cancer and at least six months between definitive surgery of the last dose of adjuvant chemotherapy and fist disease recurrence were eligible for randomisation. Chemotherapy regimens were based on the investigators’ choice of nab-pacliataxel, paclitaxel or carboplatin-gemcitabine. The trial was not designed to test the efficacy of the individual chemotherapy regimens. Crossover was not allowed.

The women in the study were about 53 years old; 75% of the treated population had PD-L1 combined positive scores greater than 1; 38% had scores of 10 or greater.  Overall, 45% received taxanes and 55 received gemcitabine plus carboplatin in the study.

The study was funded by Merck & Co.