Phase 3 Trial Shows Pembrolizumab, Chemotherapy Improve Survival in Metastatic Triple-Negative Breast Cancer

In the pivotal phase 3 KEYNOTE-355 study, pembrolizumab (Keytruda, Merck) combined with chemotherapy met one of its dual primary endpoints of progression-free survival (PFS) as a first-line treatment for patients with metastatic triple-negative breast cancer (TNBC) whose tumors expressed programmed death-ligand 1 (PD-L1).

TNBC typically has a high recurrence rate within the first 5 years following diagnosis. Because of its negative estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 tests, TNBC does not respond to therapies targeting these markers and is thus difficult to treat. TNBC is diagnosed in approximately 15%-20% of patients with breast cancer.

Pembrolizumab is an anti-PD-1 therapy that increases the ability of the body’s immune system to detect and fight tumor cells. It blocks the interaction between PD-1 and its ligands, thereby activating T lymphocytes, which may affect tumor cells as well as healthy cells. There are currently more than 1000 trials investigating pembrolizumab across a variety of cancers and settings.

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KEYNOTE-355 investigated pembrolizumab in combination with 1 of 3 different chemotherapies (investigator’s choice of nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin), compared with placebo plus 1 of the 3 chemotherapies. Patients had been diagnosed with locally recurrent inoperable or metastatic TNBC that was not previously treated with chemotherapy in the metastatic setting.

Part 1 of the trial evaluated the safety and tolerability of pembrolizumab. Thirty patients were randomized to 1 of 3 regimens and all received intravenous (IV) pembrolizumab 200 mg on day 1 of each 21-day cycle. In addition, they were randomized to receive either nab-paclitaxel 100 mg/m² IV on days 1, 8, and 15 of each cycle; paclitaxel 90 mg/m² IV on days 1, 8, and 15 of each cycle; or gemcitabine 1000 mg/m² and carboplatin area under the curve 2 on days 1 and 8 of each cycle. No new safety signals were observed, allowing the study to continue without changes.

Part 2 was double-blinded, with dual primary endpoints of overall survival and PFS. Researchers enrolled 847 patients and randomized them to receive either pembrolizumab or placebo, combined with nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin.

These results will be presented at an upcoming Medical Congress and will be discussed with regulatory authorities.

REFERENCE

Merck’s KEYTRUDA (pembrolizumab) in Combination with Chemotherapy Met Primary Endpoint of Progression-Free Survival (PFS) as First-Line Treatment for Metastatic Triple-Negative Breast Cancer (mTNBC) [news release]. Kenilworth, NJ; February 12, 2020. Merck website. https://www.mrknewsroom.com/news-release/oncology/mercks-keytruda-pembrolizumab-combination-chemotherapy-met-primary-endpoint-pr. Accessed February 14, 2020.