The first five-year follow-up of any first-line phase 3 immunotherapy trial has shown that pembrolizumab provides a durable and clinically meaningful long-term overall survival benefit relative to chemotherapy in patients with metastatic NSCLC with PD-L1 tumor proportion scores of at least 50%.

Follow-up from the KEYNOTE-024 study found that individuals treated with the humanized antibody had five-year survival rates of 31.9%, significantly better than the 16.3% observed among patients treated with platinum-based chemotherapy.

Reporting in Journal of Clinical Oncology, the international, multi-center team of researchers explained that previous analyses of KEYNOTE-024 data found first-line treatment with pembrolizumab significantly improved progression-free survival and overall survival versus chemotherapy among eligible patients.

The investigators enrolled 305 adult patients into the trial, 154 received 200 mg pembrolizumab once every three weeks for up to 35 cycles, the remaining 151 underwent investigator’s choice of platinum-based chemotherapy. 

Patients in the chemotherapy group who experienced progressive disease could cross over to pembrolizumab. The study’s primary endpoint was progression-free survival; secondary endpoints included overall survival and objective response rate.

Among patients initially assigned to chemotherapy, 99 received anti-PD-1 or PD-L1 therapy, which represented a 66.0% effective crossover rate. Interestingly, 80 patients in the pembrolizumab group (52.9%) received additional anticancer therapy; 12 of these received a second course of pembrolizumab during the study.

At the data cutoff point, 103 patients (66.9%) in the pembrolizumab group had died, compared with 123 of those in the chemotherapy group (81.5%). The median overall survival was 26.3 months for pembrolizumab patients and 13.4 months for chemotherapy patients (hazard ratio 0.62). Kaplan-Meier estimates of five-year overall survival yielded rates of 31.9% for pembrolizumab patients and 16.3% on chemotherapy.

Median progression-free survival was 7.7 months among patients in the pembrolizumab group, compared with 5.5 months for their counterparts who received chemotherapy, yielding a hazard ratio of 0.50. Similarly, objective response rate was 46.1% (71 of 154) among pembrolizumab patients and 31.1% (47 of 151) among chemotherapy patients. 

Seven patients treated with pembrolizumab (4.5%) achieved complete response; none of those in the chemotherapy group did so. The median duration of response was 29.1 months among pembrolizumab patients, compared with 6.3 months for those treated with chemotherapy.

Researchers did not identify any new safety signals. Specifically, the incidence of treatment-related adverse events was 76.6% among patients who received pembrolizumab (31.2% grade 3-5) and 90.0% among those undergoing chemotherapy (53.3% grade 3-5). 

“KEYNOTE-024 underscores the importance of pembrolizumab in first-line treatment of metastatic NSCLC,” lead author Martin Reck, MD, PhD, of the Airway Research Center North in Grosshansdorf, Germany, and colleagues wrote. “Five-year outcomes … suggest that availability of immunotherapy may result in further improvement in lung cancer survival and … pembrolizumab may be transforming metastatic NSCLC into a treatable chronic disease for patients who meet eligibility criteria.”


By Michael Vlessides, /alert Contributor