A phase 3 trial showed that Keytruda has better overall survival rates for NSCLC than chemotherapy.
When compared with chemotherapy, Keytruda (pembrolizumab) showed an improved overall survival (OS) as a frontline therapy for patients with non—small cell lung cancer (NSCLC) with high levels of PD-L1 expression in the phase 3 KEYNOTE-024 trial reported by Merck, the company developing the PD-1 inhibitor.
Keytruda was also shown to extend progression-free survival (PFS) in the first-line NSCLC setting. Based on the findings, an independent panel recommended that the trial be halted and that patients in the chemotherapy arm be allowed to cross over and receive Keytruda.
“We believe that the KEYNOTE-024 results have the potential to change the therapeutic paradigm in first-line treatment of non—small cell lung cancer,” Roger M. Perlmutter, president, Merck Research Laboratories, said in a statement. “We look forward to sharing these data with the medical community and with regulatory authorities around the world.”
The open-label phase 3 KEYNOTE-024 trial randomized 305 treatment-naive patients with advanced NSCLC to receive Keytruda or standard platinum-based chemotherapy. The trial only included patients with high levels of PD-L1 expression on their tumors, defined as 50 percent or more as measured by a central laboratory with an immunohistochemistry assay.
Keytruda was administered as a 200 mg IV infusion on the first day of each 21-day cycle until a maximum of 35 cycles or progressive disease. Patients randomized to chemotherapy received paclitaxel plus carboplatin, pemetrexed plus carboplatin, pemetrexed plus cisplatin, gemcitabine plus carboplatin, or gemcitabine plus cisplatin. Maintenance pemetrexed was allowed for patients with nonsquamous NSCLC. The primary endpoint was PFS, with secondary outcome measures including OS and overall response rate (ORR).
The safety data for Keytruda in KEYNOTE-024 were similar to previously reported outcomes with the PD-1 inhibitor in advanced NSCLC. Merck intends to submit the complete results from the study at an upcoming medical conference.
Data for frontline Keytruda in NSCLC from the phase 1 KEYNOTE-001 trial were previously published in The New England Journal of Medicine (NEJM). The KEYNOTE-001 data reported in NEJM included 495 patients with advanced NSCLC, 101 of whom were treatment-naive. All 495 patients received at least one dose of Keytruda and had an ECOG performance status equal to or less than. Keytruda was administered at two mg/kg or 10 mg/kg IV every three weeks or 10 mg/kg IV every two weeks. The median follow-up was 10.9 months.
The ORR was 24.8 percent in the 101 treatment-naive patients. The median OS was 16.2 months in these patients, and the median PFS was six months. The median duration of response was 23.3 months (range, 1.0-23.3).
Efficacy outcomes were also determined by PD-L1 status. Among treatment-naive patients with PD-L1 expression 50 percent or more, the ORR was 50 percent, the PFS was 12.5 months, and the median OS was not yet reached.
In the overall 495-patients NSCLC population, the most common all-grade adverse events (AEs) were fatigue (19.4 percent), pruritus (10.7 percent), decreased appetite (10.5 percent), rash (9.7 percent), arthralgia (9.1 percent), diarrhea (8.1 percent) and nausea (7.5 percent). The most frequently reported grade 3/4 AEs were dyspnea (3.8 percent), pneumonitis (1.8 percent), asthenia (1 percent) and decreased appetite (1 percent).
The FDA granted an accelerated approval to Keytruda in October 2015 as a treatment for patients with pretreated advanced non—small cell lung cancer across all histologies whose tumors express PD-L1. The PD-1 inhibitor was approved along with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, and is indicated for patients who progress on or after platinum-containing chemotherapy or EGFR-or ALK-targeted agents in patients harboring those mutations.