Highlights from

ASCO 2019

American Society of Clinical Oncology annual meeting

Chicago, USA 31 May - 4 June 2019

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.”

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.