The addition of pembrolizumab to chemotherapy extended OS and PFS compared with chemotherapy alone among patients with metastatic, squamous, non-small-cell lung cancer, according to results of the randomized phase 3 KEYNOTE-407 trial presented at International Association for the Study of Lung Cancer’s World Conference on Lung Cancer.
The double-blind study included 559 treatment-naive patients with metastatic, squamous NSCLC. Patients who had symptomatic central nervous system metastases, a history of noninfectious pneumonitis that required the use of glucocorticoids, active autoimmune disease or who were receiving systemic immunosuppressive treatment were excluded.
Luis Paz-Ares, MD, chair of the department of medical oncology at Hospital Doce de Octubre, associate professor at Universidad Complutense, and head of the lung cancer unit at the National Oncology Research Center in Madrid, Spain, and colleagues assigned patients to 200 mg pembrolizumab (Keytruda, Merck) or saline placebo on day 1 for up to 35 cycles. All patients also received carboplatin on day 1 and either 200 mg/m2 paclitaxel on day 1 or 100 mg/m2 nanoparticle albumin-bound (nab)-paclitaxel (Abraxane, Celgene) on days 1, 8, and 15, for the first four cycles.
OS and PFS served as primary endpoints.
Median follow-up was 7.8 months.
Results — published simultaneously in The New England Journal of Medicine — showed a consistent OS benefit, regardless of PD-L1 expression. Median OS was 15.9 months (95% CI, 13.2 to not reached) in the pembrolizumab combination arm and 11.3 months (95% CI, 9.5-14.8) in the placebo arm (HR for death = 0.64; 95% CI, 0.49-0.85).
Median PFS was 6.4 months (95% CI, 6.2-8.3) in the pembrolizumab combination arm and 4.8 months (95% CI, 4.3 to 5.7) in the placebo arm (HR for disease progression or death = 0.56; 95% CI, 0.45-0.7).
The response rate was 57.9% (95% CI, 51.9-63.8) in the pembrolizumab group and 38.4% (95% CI,32.7-44.4) in the placebo group.
In PD-L1 tumor proportion score subgroups, the response rates appeared higher among patients who received pembrolizumab compared with placebo (score < 1%, 63.2% vs. 40.4%; score of 1%-49%, 49.5% vs. 41.3%; score 50%, 60.3% vs. 32.9%).
Although differences in grade 3 or higher adverse events were not significant between the two arms (pembrolizumab, 69.8% vs. placebo, 68.2%), treatment discontinuation due to adverse events was more common among those in the pembrolizumab arm (13.3% vs. 6.4%).
The trial is being continued to evaluate long-term efficacy and safety, according to the researchers. – by Jennifer Southall
Paz-Ares, et al. Abstract MA10.08. Presented at: International Association for the Study of Lung Cancer’s World Conference on Lung Cancer; Sept. 23-26, 2018; Toronto, Canada.
Paz-Ares, et al. N Eng J Med. 2018;doi:10.1056/NEJMoa1810865.
Disclosures: The study was funded by Merck Sharp & Dohme. Paz-Ares reports grants from Merck during the conduct of the study, and personal fees from Amgen, AstraZeneca, BMS, Incyte, Lilly, Merck-Serono, Merck, Pfizer, Roche and Takeda outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.