Adding pembrolizumab to chemotherapy nearly doubles the 5-year overall survival (OS) rate in patients with advanced non-small cell lung cancer (NSCLC), according to results from the phase 3 KEYNOTE-407 trial.
In this trial, 18.4% of patients who received pembrolizumab and chemotherapy were still alive at 5 years, compared with 9.7% of patients who received chemotherapy alone. These results were published in the Journal of Clinical Oncology.
The phase 3 trial (ClinicalTrials.gov Identifier: NCT02775435) included 559 patients with previously untreated, stage IV squamous NSCLC. They were randomly assigned to receive chemotherapy with pembrolizumab (n=278) or chemotherapy with placebo (n=281).
Chemotherapy consisted of carboplatin and paclitaxel/nab-paclitaxel, given once every 3 weeks for 4 cycles. This was followed by pembrolizumab or placebo for up to 35 cycles. Patients in the placebo arm who had progressive disease (PD) could cross over to receive pembrolizumab. Patients were eligible to receive a second course of pembrolizumab for 17 cycles on PD if they completed 35 cycles and had a best overall response of stable disease or better or if they achieved a complete response (CR) after 8 or more cycles of pembrolizumab and had received 2 or more cycles beyond the initial CR assessment.
In the pembrolizumab arm, 55 patients completed 35 treatment cycles, 12 began a second course of pembrolizumab, and 109 received subsequent anticancer therapy off study. In the placebo arm, 172 patients received subsequent anticancer therapy, including 117 patients who crossed over to receive pembrolizumab monotherapy.
At a median follow-up of 56.9 months, the median OS was 17.2 months in the pembrolizumab arm and 11.6 months in the placebo arm (hazard ratio [HR], 0.71; 95% CI, 0.59-0.85). The 4-year OS rate was 21.9% in the pembrolizumab arm and 12.3% in the placebo arm. The 5-year OS rate was 18.4% and 9.7%, respectively.
Progression-free survival (PFS) was also prolonged with the addition of pembrolizumab. The median PFS was 8.0 months in the pembrolizumab arm and 5.1 months in the placebo arm (HR, 0.62; 95% CI, 0.52-0.74). The 5-year PFS rate was 10.8% in the pembrolizumab arm and 3.5% in the placebo arm.
HRs for OS and PFS favored the pembrolizumab arm across all PD-L1 tumor proportion score subgroups, the researchers noted.
Second PFS (PFS2) was improved with pembrolizumab as well (HR, 0.60; 95% CI, 0.50-0.72). The 5-year PFS2 rate was 18.1% in the pembrolizumab arm and 7.1% in the placebo arm.
There were no new treatment-related deaths since the final analysis. The rate of immune-mediated adverse events and infusion reactions was 35.6% in the pembrolizumab group and 9.3% in the placebo group.
“These data support pembrolizumab plus chemotherapy as a standard-of-care first-line treatment option for metastatic squamous NSCLC, regardless of PD-L1 expression,” the researchers concluded.
Disclosures: This study was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Novello S, Kowalski DM, Luft A, et al. Pembrolizumab plus chemotherapy in squamous non–small-cell lung cancer: 5-year update of the phase III KEYNOTE-407 study. J Clin Oncol. Published online February 3, 2023. doi:10.1200/JCO.22.01990