Merck announced the phase III KEYNOTE-181 trial investigating Keytruda as monotherapy in the second-line treatment of advanced or metastatic esophageal or esophagogastric junction carcinoma has met a primary endpoint of overall survival in patients whose tumors expressed PD-L1 (Combined Positive Score ≥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 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 and objective response rate 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.
KEYNOTE-181 is a randomized, open-label, phase III trial (ClinicalTrials.gov, NCT02564263) 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).
The Oncologic Drugs Advisory Committee held its first session since President Trump’s inauguration, with a two-day, back-to-back marathon meeting, signaling a return to business at FDA after significant upheaval at the agency.
