Merck's (MRK) KEYTRUDA Plus Chemotherapy Reduced Risk of Death by 27% vs Chemotherapy as First-Line Treatment for Metastatic Triple-Negative Breast Cancer Where Tumors Expressed PD-L1

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the final overall survival (OS) results from the pivotal Phase 3 KEYNOTE-355 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy (paclitaxel, nab-paclitaxel or gemcitabine/carboplatin) for the first-line treatment of patients with metastatic triple-negative breast cancer (mTNBC). KEYTRUDA is the first anti-PD-1 therapy in combination with chemotherapy to demonstrate a statistically significant and clinically meaningful improvement in OS for these patients.

In this study, KEYTRUDA plus chemotherapy reduced the risk of death by 27% (HR=0.73 [95% CI, 0.55-0.95]; p=0.0093) in patients with mTNBC whose tumors expressed PD-L1 (Combined Positive Score [CPS] ≥10), as compared to chemotherapy alone. There was an increase of 6.9 months in median OS with KEYTRUDA plus chemotherapy compared to chemotherapy alone (23.0 months [95% CI, 19.0-26.3] vs. 16.1 months [95% CI, 12.6-18.8], respectively). Although the trial was not powered to compare efficacy between treatment groups by different chemotherapy regimens, the increase in OS was observed for KEYTRUDA plus chemotherapy across the three chemotherapy choices. These data were presented today in an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract #LBA16).

“Metastatic TNBC has the worst survival prognosis among breast cancer subtypes, and there is an urgent need for treatment options that improve survival,” said Dr. Hope Rugo, director, Breast Oncology and Clinical Trials Education, University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center. “I am very encouraged to see these new overall survival data for the KEYTRUDA combination, demonstrating a 27% relative reduction in the risk of death compared to chemotherapy alone in patients with mTNBC whose tumors expressed PD-L1 (CPS ≥10).”

There was no statistically significant difference in OS between the treatment groups in the CPS ≥1 population; due to statistical testing hierarchy, formal testing was not performed in the intention-to-treat (ITT) population. The incidence of treatment-related adverse events (TRAEs) was similar among patients in the two treatment groups, with Grade 3-5 TRAEs occurring in 68.1% of patients in the KEYTRUDA plus chemotherapy arm and 66.9% of patients in the chemotherapy arm. Treatment-related adverse events led to discontinuation in 18.3% of patients in the KEYTRUDA plus chemotherapy arm and 11.0% of patients in the chemotherapy arm.

“With these new data, KEYNOTE-355 has now met both primary endpoints, improving progression-free and overall survival for the approximately 40% of patients from this trial with metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10),” said Dr. Vicki Goodman, vice president, clinical research, Merck Research Laboratories. “These OS data add to a strong body of evidence evaluating the use of KEYTRUDA plus chemotherapy for appropriate patients with TNBC. We remain committed to continuing to advance scientific understanding in TNBC.”

These OS data follow prior analyses from KEYNOTE-355 that showed KEYTRUDA plus chemotherapy resulted in a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemotherapy alone for the first-line treatment of patients with mTNBC whose tumors expressed PD-L1 (CPS ≥10) and supported approval of this regimen in the U.S. and Japan. In the U.S., KEYTRUDA was granted accelerated approval by the U.S. Food and Drug Administration in November 2020 and was subsequently granted regular approval in July 2021. In Europe, the Committee for Medicinal Products for Human Use of the European Medicines Agency recently adopted a positive opinion recommending approval of KEYTRUDA in combination with chemotherapy for this patient population.

Merck is rapidly advancing a broad portfolio in gynecologic and breast cancers through an extensive clinical development program for KEYTRUDA and several other investigational and approved medicines across these areas.

A compendium of presentations and posters of Merck-led studies is available here. Follow Merck on Twitter via @Merck, and keep up to date with ESMO news and updates by using the hashtag #ESMO21.

About KEYNOTE-355

KEYNOTE-355 is a randomized, two-part, placebo-controlled Phase 3 trial (ClinicalTrials.gov, NCT02819518) evaluating KEYTRUDA in combination with one of the three different chemotherapies compared with placebo plus one of the three chemotherapy regimens for the first-line treatment of mTNBC that has not been previously treated with chemotherapy in the advanced setting. The study endpoints include OS and PFS in patients whose tumors expressed PD-L1 (CPS ≥1 and CPS ≥10) and in all participants (ITT population). The other endpoints include objective response rate, duration of response, disease control rate, patient-reported outcomes and safety. Part 2 enrolled 847 patients who were randomized 2:1 to receive KEYTRUDA (200 mg every three weeks) plus chemotherapy (investigator’s choice of paclitaxel, nab-paclitaxel or gemcitabine/carboplatin) or placebo plus paclitaxel, nab-paclitaxel or gemcitabine/carboplatin.

The study population characteristics were: median age of 53 years (range, 22 to 85), 21% age 65 or older; 100% female; 68% white, 21% Asian and 4% Black; 59% Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, and 41% ECOG PS of 1; and 68% were post-menopausal. Among enrolled patients in each treatment group, approximately 75% had tumors expressing PD-L1 with CPS ≥1 (n=425/566 for KEYTRUDA plus chemotherapy; n=211/281 for chemotherapy alone), and approximately 38% had tumors expressing PD-L1 with CPS ≥10 (n=220/566 for KEYTRUDA plus chemotherapy; n=103/281 for chemotherapy alone).

Immune-mediated adverse reactions (AEs) of any grade occurred in 26.5% of patients receiving KEYTRUDA plus chemotherapy and 6.4% of patients receiving chemotherapy alone. For patients receiving KEYTRUDA plus chemotherapy, the most common immune-mediated AE (occurring in ≥10% of patients) was hypothyroidism (15.8%). There were two treatment-related deaths due to acute kidney injury and pneumonia in patients receiving KEYTRUDA plus chemotherapy; neither was considered immune-mediated.

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