The phase I KEYNOTE-001 study reports that in patients with advanced non-small cell lung cancer (NSCLC), pembrolizumab (Keytruda®, Merck) increases five-year overall survival.
"For patients with non-small cell lung cancer (NSCLC), median overall survival… and five-year survival rates have historically been poor," Edward B. Garon, MD, MS, Health Sciences Associate Clinical Professor of Medicine at the University of California, Los Angeles (UCLA), and colleagues comment in their publication in the Journal of Clinical Oncology. "In the United States, five-year survival between 2008 and 2014 was 24% for all patients with NSCLC and 5.5% for those with distant metastases." The results with pembrolizumab for advanced-stage patients in the KEYNOTE-001 study demonstrate a substantial improvement over these statistics.
Pembrolizumab is a monoclonal antibody that targets programmed cell death protein 1 (PD-1), blocking its receptor. In April, the FDA added a pembrolizumab indication for patients with stage III NSCLC ineligible for surgical resection or definitive chemoradiation; previously, pembrolizumab's only indication in NSCLC was for metastatic disease. This immunotherapeutic agent is also used for inoperable or metastatic melanoma, for second-line treatment of head and neck squamous cell carcinoma, and for refractory classic Hodgkin lymphoma.
For the KEYNOTE-001 study, 550 patients with advanced NSCLC expressing programmed death ligand 1 (PD-L1), including 101 treatment-naive and 449 previously treated patients, were administered intravenous pembrolizumab 2 mg/kg every three weeks or 10 mg/kg every two or three weeks. The trial's primary efficacy end point was objective response rate, with secondary end points of overall survival and duration of response. The median follow-up was at 60.6 months.
At the time of data cutoff on November 5, 2018, 450 patients (82%) had died. Pembrolizumab produced a median overall survival of 22.3 months in treatment-naive patients and 10.5 months in previously treated patients, with an estimated five-year overall survival of 23.2% for treatment-naive patients and 15.5% for previously treated patients. In patients with a PD-L1 tumor proportion score of 50% or higher, pembrolizumab produced five-year overall survival rates of 29.6% in treatment-naive patients and 25.0% in previously treated patients. No late-onset grade 4 or 5 treatment-related adverse events occurred; since the three-year analysis, only three new grade 3 treatment-related adverse events occurred—hypertension, glucose intolerance, and hypersensitivity reaction—all of which were resolved.
"Five-year outcomes from the KEYNOTE-001 study demonstrate that pembrolizumab provides long-term [overall survival] benefit and durable responses, with tolerable safety for treatment-naive and previously treated patients with advanced PD-L1–expressing NSCLC," conclude Dr. Garon and colleagues. "In the context of low historical five-year survival in advanced NSCLC, these data demonstrate the potential of pembrolizumab treatment to improve long-term outcomes for patients with advanced NSCLC."
For More Information
Garon EB, Hellmann MD, Rizvi NA, et al (2019). 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. [Epub ahead of print] DOI:10.1200/JCO.19.00934
Image credit: Scott Wilkinson and Adam Marcus. Courtesy of the National Cancer Institute / Winship Cancer Center at Emory University