As reported in the Journal of Clinical Oncology by Roy S. Herbst, MD, PhD, and colleagues, long-term follow-up of patients with previously treated advanced programmed cell death ligand 1 (PD-L1)-positive non–small cell lung cancer (NSCLC) in the KEYNOTE-010 trial has shown a continued survival benefit with pembrolizumab vs docetaxel and the ability to obtain disease control with pembrolizumab retreatment.
Roy S. Herbst, MD, PhD
Study Details
The primary analysis from the trial showed improved overall survival with pembrolizumab vs docetaxel in patients with PD-L1 tumor proportion score (TPS) ≥ 50% and ≥ 1%. The current report evaluated long-term outcomes in study patients, including after 35 cycles/2 years or second-course pembrolizumab.
In the trial, 1,033 patients were randomly assigned to receive pembrolizumab (n = 690) for up to 35 cycles/2 years at 2 mg/kg (n = 344) or 10 mg/kg (n = 346) every 3 weeks or docetaxel at 75 mg/m2 every 3 weeks (n = 343). Eligible patients with disease progression after 35 cycles/2 years of pembrolizumab could receive a second course of pembrolizumab for up to 17 cycles. In the current analysis, pembrolizumab dose groups were pooled, since no between-dose differences were observed in the primary analysis.
Long-Term Outcomes
After a median follow-up of 42.6 months (range = 35.2–53.2 months), the pembrolizumab group continued to exhibit significantly improved overall survival vs the docetaxel group in both the TPS ≥ 50% (hazard ratio [HR] = 0.53, P < .00001) and TPS ≥ 1% groups (HR = 0.69, P < .00001). For the two TPS groups, estimated 3-year overall survival rates were 34.5% vs 12.7% and 22.9% vs 11.0%. Estimated 3-year progression-free survival in the TPS groups was 21.9% vs 1.2% (HR = 0.57, P < .00001) and 12.7% vs 1.0% (HR = 0.83, P = .005). Overall, grade ≥ 3 treatment-related adverse events occurred in 16% of patients treated with pembrolizumab vs 37% of patients treated with docetaxel.
KEY POINTS
- A survival advantage of pembrolizumab treatment was maintained over long-term follow-up.
- Objective response or stable disease was achieved in most patients receiving retreatment with pembrolizumab.
A total of 7 of 9 patients in the pembrolizumab group completed an initial 35 cycles/2 years of treatment. Objective response was observed in 75 patients (95%), and 48 (64%) had ongoing response at the end of treatment. Overall survival and progression-free survival rates at 12 months after treatment completion were 98.7% and 72.5%. Among these 79 patients, grade ≥ 3 treatment-related adverse events occurred in 17.7%.
Retreatment Outcomes
A total of 14 patients received a second course of pembrolizumab, with 5 completing 17 cycles. Partial response was observed in six (43%) and stable disease in five (36%). As of data cutoff, 11 patients (78.6%) remained alive.
The investigators concluded, “Pembrolizumab provided long-term [overall survival] benefit over docetaxel, with manageable safety, durable responses among patients receiving 2 years of treatment, and disease control with second-course treatment, further supporting pembrolizumab for previously treated, PD-L1‒expressing advanced NSCLC.”
Dr. Herbst, of Yale Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme, a subsidiary of Merck. For full disclosures of the study authors, visit ascopubs.org.
