Five-year overall survival (OS) for patients enrolled in the phase Ib KEYNOTE-001 study were reported by Edward B. Garon of the David Geffen School of Medicine, University of California, Los Angeles, Santa Monica, CA, US at 2019 ASCO Annual Meeting and simultaneously published in the Journal of Clinical Oncology. The KEYNOTE-001 is the first trial evaluating pembrolizumab in advanced non-small cell lung cancer (NSCLC).
Pembrolizumab monotherapy provided durable antitumour activity and high five-year OS rates in patients with treatment-naïve or previously treated advanced NSCLC. The five-year OS rate exceeded 25% among patients with a PD-L1 tumour proportion score (TPS) of 50% or greater. Pembrolizumab had a tolerable long-term safety profile with little evidence of late-onset or new toxicity.
The KEYNOTE-001 investigators reported previously that pembrolizumab monotherapy demonstrate durable antitumour activity in advanced PD-L1–expressing NSCLC. At ASCO 2019 Annual Meeting, they presented five-year OS data that provide the longest efficacy/safety follow-up for NSCLC patients treated with pembrolizumab.
All patients had confirmed locally advanced/metastatic NSCLC and provided a contemporaneous tumour sample for PD-L1 evaluation by immunohistochemistry using the 22C3 antibody. Patients received pembrolizumab 2 mg/kg every 3 weeks or 10 mg/kg every 2 or 3 weeks. The primary efficacy endpoint was overall response rate (ORR) and OS was a secondary endpoint.
In total 550 patients were enrolled from whom 101 treatment-naïve and 449 previously treated. As of 5 November 2018, as data cut-off, median (range) follow-up was 60.6 months; 82% (450 of 550 patients) had died.
Median OS was 22.3 months in treatment-naïve patients and 10.5 months in previously treated patients. Estimated five-year OS rates were 23.2% for treatment-naïve patients and 15.5% for previously treated patients. In patients with a PD-L1 TPS of 50% or greater, five-year OS was 29.6% and 25.0% in treatment-naïve and previously treated patients, respectively.
The ORR by investigator per immune-related response criteria was 42% for treatment-naïve patients and 23% for previously treated patients. Median duration of response was 16.8 months and 38.9 months, respectively.
Immune-mediated adverse events had occurred in 17% of patients at 5 year, similar to the incidence reported at 3-year follow-up. Compared with analysis at 3 years, only three new-onset treatment-related grade 3 adverse events occurred: hypertension, glucose intolerance, and hypersensitivity reaction. No late-onset grade 4 or 5 treatment-related adverse events occurred.
The authors concluded that in KEYNOTE-001, five-year OS rate was 23.2% in treatment-naïve patients and 15.5% in previously treated patients with advanced NSCLC treated with pembrolizumab, compared to a historical rate of approximately 5% per SEER 2008–2014 data, prior to the introduction of anti–PD-1 therapy. Five-year OS rate was at least 25% in patients with PD-L1 TPS ≥50% in both patient populations in KEYNOTE-001.
The study was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., (Kenilworth, NJ).
Garon EB, Hellmann MD, Costa EC, et al. Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001. J Clin Oncol 37, 2019 (suppl; abstr LBA9015).
Garon EB, Hellmann MD, Rizvi NA, et al. Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J Clin Oncol, Published online on 2 June, 2019. DOI: 10.1200/JCO.19.00934.