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](/media/14011973/101-herbst.jpg)
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.