Merck has revealved that the Phase 3 Keynote-181 trial investigating Keytruda, Merck’s anti-PD-1 therapy, as monotherapy in the second-line treatment of advanced or metastatic esophageal or esophagogastric junction carcinoma has met a primary endpoint of overall survival (OS) in patients whose tumors expressed PD-L1 (Combined Positive Score [CPS] ≥10).
In this pivotal study, treatment with Keytruda resulted in a statistically significant improvement in OS compared to chemotherapy (paclitaxel, docetaxel, or irinotecan) in patients with CPS ≥10, regardless of histology. The primary endpoint of OS was also evaluated in patients with squamous cell histology and in the entire intention-to-treat (ITT) study population.
While directionally favorable, statistical significance for OS was not met in these two patient groups. Per the statistical analysis plan, the key secondary endpoints of progression-free survival (PFS) and objective response rate (ORR) were not formally tested, as OS was not reached in the full ITT study population. The safety profile of Keytruda in this trial was consistent with that observed in previously reported studies. Results will be presented at an upcoming medical meeting and will be submitted to regulatory authorities worldwide.
“In this pivotal trial, Keytruda resulted in a statistically significant and clinically meaningful improvement over standard chemotherapy in overall survival for patients with advanced esophageal or esophagogastric junction carcinoma whose tumors express PD-L1 with a CPS of 10 or greater. This marks the sixth tumor type where Keytruda has demonstrated a survival benefit, and represents the first time an anti-PD-1 therapy has achieved overall survival for this patient population,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We are encouraged by these results of Keytruda as monotherapy in previously-treated patients, and look forward to continuing our research efforts in this significant area of unmet need with our ongoing Phase 3 trial, Keynote-590, evaluating Keytruda in combination with chemotherapy as a first-line treatment for patients with esophageal carcinoma.”
Keynote-181 is a randomized, open-label, Phase 3 trial investigating Keytruda monotherapy compared to chemotherapy in patients with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus, or Siewert type I adenocarcinoma of the esophagogastric junction that has progressed after first-line standard therapy. The primary endpoint was OS (evaluated in all patients as well as in patients with PD-L1 CPS ≥10 and in patients with squamous cell carcinoma).
Secondary endpoints were PFS, ORR, and safety/tolerability. The study enrolled more than 600 patients who were randomized 1:1 to receive either Keytruda (200 mg fixed dose every three weeks) or investigator’s choice of any of the following chemotherapy regimens, all given intravenously: docetaxel (75 mg/m^2 on Day 1 of each 21-day cycle), paclitaxel (80-100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle), or irinotecan (80 mg/m^2 on Day 1 of each 14-day cycle).
About Esophageal Cancer
Esophageal cancer, a type of cancer that is particularly difficult to treat, begins in the inner layer (mucosa) of the esophagus and grows outward. There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. Globally, esophageal cancer is the seventh most commonly diagnosed cancer. This year, an estimated 17,290 adults in the United States will be diagnosed with esophageal cancer, and 15,850 deaths from this disease will occur. Worldwide, there are estimated to be over 572,000 new cases of esophageal cancer and approximately 508,000 deaths resulting from this disease in 2018 alone.
Filed Under: Oncology