Pembrolizumab monotherapy leads to 5-year survival in some patients with NSCLC

Medical writer: Jasenka Piljac Žegarac, PhD

Pembrolizumab monotherapy induces a durable anti-tumour response in patients with advanced non–small cell lung cancer (NSCLC), according to 5-year data from KEYNOTE-001—the first clinical trial evaluating pembrolizumab in advanced NSCLC (Abstract LBA9015).

“This is the longest follow-up for a large population of treatment-naive and previously treated patients with NSCLC treated with an inhibitor of the PD-1 immune checkpoint,” lead author Edward B. Garon, MD, MS, of the David Geffen School of Medicine, University of California/TRIO-US Network, said. “Not only were we able to induce durable responses, but now we have 5-year follow-up for this patient population.”

KEYNOTE-001 is a phase Ib, randomized, open-label study evaluating pembrolizumab in several different types of locally advanced or metastatic cancers. Cohorts C and F aimed to assess the safety, tolerability, and efficacy of pembrolizumab in patients with locally advanced or metastatic NSCLC. It enrolled 101 treatment-naive and 449 previously treated patients whose -s were subjected to PD-L1 evaluation by immunohistochemistry. Patients received pembrolizumab according to one of three dosing schedules: 2 mg/kg every 3 weeks or 10 mg/kg every 2 weeks or every 3 weeks. Objective response rate (ORR) served as the primary endpoint, and overall survival (OS) was the secondary endpoint.

At the data cut off, the median follow-up was 60.6 (51.8 to 77.9) months, and 82% of patients (450/550) had died. Estimated 5-year survival was 15.5% for previously treated patients and 23.2% for treatment-naive patients. ORR (by investigator per Independent Regulatory Review Commission) was 23% (95% CI [19, 27]) for previously treated patients and 42% (95% CI [32, 52]) for treatment-naive patients. Median duration of response was 38.9 and 16.8 months in the two patient groups, respectively.

“At the beginning of my career in 2006, the estimated 5-year survival of a patient with metastatic NSCLC was considered to be less than 1%,” Dr. Garon said. “Back in the spring of 2012 when we started the first lung cancer cohort in KEYNOTE-001, it would have been hard for us to believe that we would have more than 15% of pre-treated patients, and close to a quarter of treatment-naive patients, alive 5 years out. [This is] very exciting for our field.”

At the 5-year mark, 17% of patients reported immune-mediated adverse events (AEs), which was similar to the AE incidence reported at the 3-year follow-up.

“We now have patients who have been on pembrolizumab for almost 7 years, and what is reassuring is that there does not appear to be a significant increase in AEs over time,” Dr. Garon said. “The optimal duration of therapy is something that is still being explored.”



Posted on 15 July 201925 March 2021