Pembrolizumab Plus Chemotherapy for Advanced Triple-Negative Breast Cancer: KEYNOTE-355

By: Justine Landin, PhD
Posted: Thursday, December 22, 2022

Patients with advanced triple-negative breast cancer whose tumors overexpress PD-L1 may clinically benefit from the addition of pembrolizumab to standard chemotherapy, according to Javier Cortes, MD, PhD, of Universidad Europea de Madrid, and colleagues. In fact, longer overall survival was observed when these patients were treated with pembrolizumab plus chemotherapy compared with chemotherapy alone. The findings of the phase III KEYNOTE-355 trial were published in The New England Journal of Medicine.

“These observations suggest a differential role of baseline tumor PD-L1 expression in the efficacy of immune checkpoint inhibition for early-stage as compared with late-stage disease,” stated the study investigators.

Patients with untreated locally recurrent inoperable or metastatic triple-negative breast cancer were enrolled (n = 847) and randomly assigned to receive pembrolizumab (200 mg, every 3 weeks) in addition to investigator’s choice of chemotherapy (n = 566) or placebo plus chemotherapy (n = 281). Tumors were evaluated for the overall rate of PD-L1 expression, as well as the ratio of PD-L1 tumor cells compared with the total number of viable tumor cells, to identify a combined positive score (CPS). Patients who expressed PD-L1 with a CPS of at least 10 (CPS-10 subgroup) were compared with patients with PD-L1 expression and CPS levels of at least 1 (CPS-1 subgroup), and the intention-to-treat population.

At the median follow-up of 44.1 months, overall survival was increased in patients in the CPS-10 subgroup (23.0 months) compared with the CPS-1 subgroup (16.1 months). The median overall survival for the CPS-10 subgroup was 23.0 months with pembrolizumab plus chemotherapy and 16.1 months with placebo plus chemotherapy (P = .018). According to the investigators, there was no significant difference in median overall survival between combination therapy versus monotherapy for patients in the CPS-1 subgroup or in the intention-to-treat population.

Disclosure: For full disclosures of the study authors, visit nejm.org.

The New England Journal of Medicine

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