PD-1 Inhibitor Doubled Survival in Treatment-Naive Patients With mNSCLC

Overall survival (OS) in patients being treated with pembrolizumab, a programmed death-1 (PD-1) inhibitor, for metastatic non—small cell lung cancer (mNSCLC) that expressed high levels of the programmed death ligand-1 (PD-L1) protein was double that of patients who were treated with chemotherapy. These 2-year follow-up results from the Keynote-024 trial were presented at the 18th World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Yokohama, Japan.

The study assigned 305 treatment-naïve patients with mNSCLC to receive pembrolizumab (n = 154) or platinum-based chemotherapy (n = 151). In addition to being treatment-naïve, inclusion criteria restricted patients who had a sensitizing mutation in the epidermal growth factor receptor or an ALK translocation from participating in the trial. Further, only patients whose tumors expressed high levels of PD-L1 (tumor proportion score of 50% or more) were allowed to participate. The primary trial endpoint was progression-free survival; OS, overall response rate (ORR), and safety were secondary endpoints. The study had a crossover rate of 62.3%, a majority of which was accounted for in the study protocol.

At a 30-month follow up, median OS was 30.0 months for pembrolizumab (95% CI, 18.3—not reached), double that of the chemotherapy-treated group, which had a median OS of 14.2 months (95% CI, 9.8–19.0). Pembrolizumab also reduced the risk of death by 37% compared with chemotherapy (hazard ratio, 0.63 [95% CI, 0.47-0.86]; nominal P = .002). The 24-month OS rate was 51.5% among patients treated with pembrolizumab, compared with 34.5% among those treated with chemotherapy.

The other secondary endpoint of ORR was also higher in the pembrolizumab-treated group: 45.5% (95% CI, 37.4-53.7) compared with 29.8% (95% CI, 22.6-37.8) in the chemotherapy group.

No new safety signals were noted with pembrolizumab—a little over 31% of patients experienced Grade 3-5 treatment-related adverse events, including diarrhea, fatigue, pyrexia, pruritus, nausea, decreased appetite, and rash.

“As we continue to see updated findings from this study of patients with non-small cell lung cancer in the first-line setting, practitioners are gaining valuable insights into the longer-term clinical benefit of Keytruda,” said senior author Martin Reck, MD, PhD, head of the department of thoracic oncology, LungenClinic Grosshansdorf, Germany in a statement. “The significant overall survival findings observed in Keynote-024, which includes patients who have a poor prognosis, reinforce the use of Keytruda in appropriate patients in the first-line treatment of this disease.”

Speaking with The American Journal of Managed Care^®, Naiyer A. Rizvi, MD, director of thoracic oncology and immunotherapeutics at Columbia University Medical Center, emphasized the importance of targeting a "subset" of patients with lung cancer with PD-1 inhibitors, since it is such a heterogenous disease.