Phase 3 Trial of Pembrolizumab Met Primary Endpoint of Overall Survival In Certain Patients With Triple-Negative Breast Cancer

Pembrolizumab (Keytruda, Merck), in combination with chemotherapy, has shown positive overall survival (OS) results in patients with metastatic triple-negative breast cancer (TNBC), according to the results of the phase 3 KEYNOTE-355 trial. Pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in OS for patients whose tumors expressed PD-L1 with a combined positive score ≥10 compared to chemotherapy alone, according to the study.

TNBC is an aggressive breast cancer that typically has a high recurrence rate within 5 years post-diagnosis. Whereas some patients with breast cancer may test positive for estrogen receptors, progesterone receptors, or overexpression of human epidermal growth factor receptor 2 (HER2), patients with TNBC test negative for all 3. Approximately 10% to 15% of patients with breast cancer receive a diagnosis of TNBC, and it is more common in patients under 40 years of age, who are African American, or who have a BRCA1 mutation.

A previous interim analysis showed that pembrolizumab, in combination with chemotherapy, improved progression-free survival for these patients compared to chemotherapy alone. Pembrolizumab is currently approved by the FDA, in combination with chemotherapy, for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 as determined by an FDA-approved test.

“In the fight against triple-negative breast cancer, the subtype with the worst survival prognosis, new options that can extend the lives of patients are urgently needed,” said Vicki Goodman, MD, vice president of clinical research at Merck Research Laboratories, in a press release. “These new overall survival results confirm that Keytruda in combination with chemotherapy represents an important treatment option for certain patients with metastatic TNBC. We thank the patients and investigators who have allowed us to evaluate innovative treatment approaches, anchored by Keytruda, across multiple settings and stages of TNBC.”

The KEYNOTE-355 trial is a randomized, 2-part, placebo-controlled phase 3 trial evaluating pembrolizumab in combination with 1 of 3 chemotherapies compared to placebo combined with 1 of the chemotherapy regimens in the treatment of locally recurrent inoperable or metastatic TNBC that has not been previously treated with chemotherapy in the advanced setting. The study enrolled 847 patients who were randomized 2:1 to receive pembrolizumab in combination with chemotherapy or placebo combined with chemotherapy.

Yesterday, the FDA approved pembrolizumab for the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as a neoadjuvant treatment, and then continued as a single agent after surgery.

REFERENCE

Merck announces phase 3 KEYNOTE-355 trial met primary endpoint of overall survival (OS) in patients with metastatic triple-negative breast cancer whose tumors expressed PD-L1 (CPS ≥10) [news release]. Merck; July 27, 2021. Accessed July 27, 2021. https://www.merck.com/news/merck-announces-phase-3-keynote-355-trial-met-primary-endpoint-of-overall-survival-os-in-patients-with-metastatic-triple-negative-breast-cancer-whose-tumors-expressed-pd-l1-cps-%e2%89%a510/