Merck & Co. said Wednesday that Keytruda (pembrolizumab) significantly improved overall survival (OS) compared to chemotherapy as monotherapy in the second-line treatment of advanced or metastatic oesophageal or oesophagogastric junction carcinoma in patients whose tumours expressed PD-L1 with a combined positive score (CPS) of at least 10. Roy Baynes, chief medical officer at Merck Research Laboratories, said the Phase III KEYNOTE-181 trial "represents the first time an anti-PD-1 therapy has achieved overall survival for this patient population."
KEYNOTE-181 enrolled more than 600 patients with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the oesophagus, or Siewert type I adenocarcinoma of the oesophagogastric junction that has progressed after first-line standard therapy. Participants were randomised to receive either Keytruda monotherapy or investigator's choice of various intravenous chemotherapy regimens.
The primary OS endpoint was evaluated in patients expressing PD-L1 with a CPS of 10 or more, as well as in the entire intention-to-treat (ITT) study population and in patients with squamous cell carcinoma. Merck noted that "while directionally favourable, statistical significance for OS was not met in [the ITT and squamous cell carcinoma] groups." Secondary goals were progression-free survival (PFS) and objective response rate, however the company stated that neither were formally tested as OS was not reached in the full ITT population. Merck added that Keytruda's safety profile in the trial was consistent with that observed in previously reported studies. KEYNOTE-181 results will be presented at an upcoming medical meeting.
Baynes noted "this marks the sixth tumour type where Keytruda has demonstrated a survival benefit," adding that Merck will be "continuing our research efforts in this significant area of unmet need with our ongoing Phase III trial, KEYNOTE-590, evaluating Keytruda in combination with chemotherapy as a first-line treatment for patients with oesophageal carcinoma."
In September 2017, the FDA granted Keytruda accelerated approval as a third-line treatment for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumours express PD-L1 with a CPS of at least 1. Merck later announced that Keytruda had failed to significantly prolong OS and PFS in the Phase III KEYNOTE-061 trial of patients with advanced gastric or GEJ adenocarcinoma.
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