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Early treatment of metastatic triple-negative breast cancer with pembrolizumab (Keytruda) provided a progression-free survival benefit to women whose tumors had high levels of the agent's target PD-L1 when compared with standard-of-care chemotherapy alone, researchers reported at the .

Median progression-free survival was 9.7 months with pembrolizumab in addition to a chemotherapy regimen selected by the treating physicians compared with 5.6 months with chemotherapy alone (P=0.0012), reported Javier Cortes, MD, PhD, head of the Breast Cancer Program at IOB Institute of Oncology in Barcelona. Patients were stratified by the level of PD-L1 expression, and this group of patients had a combined positive score of 10 or greater.

The advantage met a prespecified boundary for statistical significance of P=0.00411, he said in his prerecorded presentation.

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

The different stratifications were the co-primary endpoints of the KEYNOTE-355 study. Cortes said there were no statistically significant 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 new development for women with triple-negative breast cancer because treatment options have been limited to chemotherapy, said Alice Police, MD, regional director of breast care for Northwell Health Cancer Institute in Sleepy Hollow, New York, who was not involved with the study.

"The great thing about pembrolizumab is that it is the first really targeted therapy for triple-negative breast cancer," she told 名媛直播. "This is an amazing and much needed development in the treatment of triple-negative breast cancer. We finally have a targeted therapy that shows some good results. This is some of the first evidence that shows that it works."

However, 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, to turn it into a chronic disease."

In the study, conducted from January 2017 to June 2018, Cortes and colleagues recruited 847 patients and randomly assigned 566 patients to receive pembrolizumab plus chemotherapy, while 281 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.

PD-L1 expression was assessed at the central laboratory and characterized by the combined positive score, defined as the number of PD-L1-positive cells, which included tumor cells, lymphocytes, and macrophages, divided by the total number of tumor cells by 100. Patients nevertheless were eligible for the study regardless of PD-L1 status, Cortes said.

In KEYNOTE-355, patients with previously untreated metastatic triple-negative breast cancer and at least 6 months between definite surgery or last dose of adjuvant chemotherapy, whatever was last, and first disease recurrence were randomized. Chemotherapy regimens were based on the investigators' choice of nab-paclitaxel, paclitaxel, or carboplatin-gemcitabine. The trial was not designed to test the efficacy of the individual chemotherapy regimens, and 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, and 38% had scores of 10 or greater. Overall, 45% received taxanes and 55 received gemcitabine plus carboplatin in the study.

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