In a health-related quality of life analysis from the phase III KEYNOTE-407 trial reported in the Journal of Clinical Oncology, Mazières et al found that the patients with metastatic squamous non–small cell lung cancer (NSCLC) who received pembrolizumab in addition to chemotherapy had better outcomes vs those receiving placebo plus chemotherapy.
KEYNOTE-407 supported the October 2018 approval of pembrolizumab in combination with carboplatin/paclitaxel or carboplatin/nab-paclitaxel for the first-line treatment of patients with metastatic squamous NSCLC.
“Addition of pembrolizumab to chemotherapy maintained or improved health-related quality of life measurements relative to baseline and improved health-related quality of life vs chemotherapy alone at weeks 9 and 18. These results support use of pembrolizumab plus chemotherapy as first-line therapy for metastatic squamous NSCLC.”— Mazières et al
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Study Details
In the trial, 559 patients were randomly assigned to receive four cycles of pembrolizumab at 200 mg (n = 278) or placebo (n = 281) every 3 weeks in addition to carboplatin plus investigator’s choice of paclitaxel or nab-paclitaxel, followed by pembrolizumab or placebo for an additional 31 cycles. The trial showed that the addition of pembrolizumab to chemotherapy significantly improved overall and progression-free survival and objective response rate.
The main patient-reported outcomes were: change from baseline to week 9 and 18 (ie, during and after platinum/taxane therapy) in the EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) global health status/quality of life (GHS/QoL) score; and time to deterioration in the composite endpoint of cough, chest pain, or dyspnea from the QLQ-C30 and Quality of Life Questionnaire-Lung Cancer Module 13 (QLQ-LC13). Patient-reported outcome scores for individual patients were categorized as improved or deteriorated with a ≥ 10-point change (considered clinically meaningful) on each instrument.
Key Findings
A total of 554 patients and 553 patients completed one or more QLQ-C30 and one or more QLQ-LC13 assessment.
Least squares mean change from baseline in GHS/QoL score was +1.8 points in the pembrolizumab/combination group vs -1.8 points in the placebo/combination group at week 9 and +4.3 points vs -0.57 points at week 18.
Between-group differences were 3.6 points at week 9 (nominal P = .0337) and 4.9 at 18 weeks (nominal P = .0060). The difference at week 18 was considered clinically meaningful in favor of the pembrolizumab/combination group.
Proportions of patients in the pembrolizumab vs placebo groups with deterioration in GHS/QoL status were 26.1% vs 29.5% at week 9 and 22.8% vs 31.3% at week 18. Proportions with improvement were 30.4% vs 24.5% at week 9 and 36.2% vs 27.7% at week 18.
Median time to deterioration in the composite endpoint of cough, chest pain, or dyspnea was not reached in either group, with the hazard ratio (0.79, 95% confidence interval = 0.58–1.06, nominal P = .125) favoring the pembrolizumab group. With a median follow-up of 7.8 months, deterioration was observed in 29.3% of the pembrolizumab group vs 33.8% of the placebo group.
The investigators concluded, “Addition of pembrolizumab to chemotherapy maintained or improved health-related quality of life measurements relative to baseline and improved health-related quality of life vs chemotherapy alone at weeks 9 and 18. These results support use of pembrolizumab plus chemotherapy as first-line therapy for metastatic squamous NSCLC.”
Julien Mazières, MD, PhD, of the Thoracic Oncology Department, Hôpital Larrey, CHU Toulouse, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit jco.ascopubs.org.
