Results of the 2-year follow-up analysis of the pivotal KEYNOTE-024 trial were recently published in the Journal of Clinical Oncology.
A long-term analysis of the pivotal KEYNOTE-024 trial showed that pembrolizumab continues to improve survival and have less toxicity compared with platinum-based chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) that is positive for programmed death ligand 1 (PD-L1). The results were published in the Journal of Clinical Oncology.
The initial results of the KEYNOTE-024 trial revealed that pembrolizumab had superior progression-free survival and estimated overall survival (OS) compared with chemotherapy. This 2-year follow-up analysis of the trial provides confirmation that pembrolizumab improves OS long-term.
“We were expecting that survival would be better [with pembrolizumab] and continue to be with more follow-up,” said Ashish Saxena, MD, PhD, an oncologist at Weill Cornell Medicine and NewYork-Presbyterian, during an interview with Cancer Network. “I can’t say there was anything particularly new or surprising, just confirmatory, which is always good.”
KEYNOTE-024 is a randomized, open-label, phase III trial evaluating pembrolizumab as a first-line treatment for patients with stage IV NSCLC and PD-L1 expression on at least 50% of tumor cells. Eligible patients had no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocations. The trial enrolled 305 patients and randomly assigned them to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or 4 to 6 cycles of platinum-based chemotherapy, per the investigator’s choice.
At a median follow-up of 25.2 months, a total of 169 patients had died, 73 in the pembrolizumab group and 96 in the chemotherapy group. The median OS for patients who received pembrolizumab was nearly 16 months longer than that of patients who received chemotherapy (30.0 vs 14.2 months). Patients who received pembrolizumab also had a 37% lower likelihood of dying (hazard ratio [HR], 0.63; 95% CI, 0.47–0.86). At 2 years, a higher portion of patients in the pembrolizumab group remained alive compared with the chemotherapy group (51.5% vs 34.5%).
Crossover was permitted, with 82 patients crossing over from the chemotherapy group to the pembrolizumab group. A total of 17 patients (20.7%) who crossed over achieved an objective response, and 19 patients (23.2%) achieved stable disease.
When crossover was accounted for in the analysis, the difference in median OS between treatment groups widened further: patients who received pembrolizumab had a 51% lower likelihood of dying than patients who received chemotherapy (HR, 0.49; 95% CI, 0.34–0.69).
The long-term safety profile also continued to favor pembrolizumab, with the immunotherapeutic resulting in fewer grade 3 to 5 treatment-related adverse events (AEs) than chemotherapy (31.2% vs 53.3%). For the pembrolizumab group, diarrhea (3.9%) and pneumonitis (3.2%) were the most frequent grade 3 to 5 treatment-related AEs.
Commenting on the safety profile of pembrolizumab, Saxena said, “[Pembrolizumab] is still overall better tolerated than chemotherapy, and the types of side effects were pretty consistent with what we’ve been seeing in other studies.”
Saxena said the long-term results do not “really change anything” because pembrolizumab is already approved by the US Food and Drug Administration as a first-line single agent in patients with PD-L1–positive advanced NSCLC without EGFR or ALK aberrations. He said the results provide “more confidence” in the initial finding that pembrolizumab conferred a survival advantage and “some actual numbers in terms of the overall survival.”