When used as first-line therapy for advanced non–small cell lung cancer (NSCLC), pembrolizumab (Keytruda) yields better health-related quality of life than platinum-based chemotherapy, suggest new data from the randomized phase III KEYNOTE-024 trial.1
After 15 weeks of treatment, changes in scores on a European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire differed by 7.8 points in favor of pembrolizumab, an antibody that targets the programmed cell death protein 1 (PD-1) receptor, first author Julie Renee Brahmer, MD, reported in a plenary session and press conference at the 17th World Conference on Lung Cancer.
Pembrolizumab may be a new standard of care for the first-line treatment of advanced NSCLC with a PD-L1 expression [tumor proportion score] of greater than or equal to 50%.— Julie Renee Brahmer, MD
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“Some people might argue that a 7-point difference might not be clinically significant,” she commented. “But when you have patients treated with a disease such as NSCLC, where you have a lot of symptoms, a smaller change may be clinically significant, and this is supported by some publications that say one could consider at least a 4-point difference as clinically significant.”
The pembrolizumab group also had a one-third lower risk of deterioration in the symptoms of cough, chest pain, and dyspnea when compared with the chemotherapy group.
These data add to the trial’s favorable efficacy findings in terms of progression-free survival (hazard ratio [HR] = 0.50) and overall survival (HR = 0.60), which were reported earlier in the year2 and led to U.S. Food and Drug Administration (FDA) approval of pembrolizu-mab as the first immune checkpoint inhibitor for use in the first-line setting in patients having programmed cell death ligand 1 (PD-L1)–rich tumors without sensitizing epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) aberrations.
“Combined with the superior progression-free survival and overall survival, as well as manageable safety profile, pembrolizumab may be a new standard of care for the first-line treatment of advanced [NSCLC] with a PD-L1 expression TPS [tumor proportion score] of greater than or equal to 50%,” concluded Dr. Brahmer, who is Associate Professor of Oncology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore.
In KEYNOTE-024, a total of 350 patients with PD-L1–rich advanced NSCLC lacking EGFR and ALK aberrations were randomized to receive pembrolizumab every 3 weeks or platinum-containing chemotherapy doublet for 4 to 6 cycles, with crossover to pembrolizumab permitted at disease progression. The protocol prespecified exploratory analyses of patient-reported outcomes. Patients completed questionnaires electronically at the first 3 cycles of therapy and every 9 weeks thereafter.
The investigators used two EORTC quality-of-life questionnaires: the 30-item core quality-of-life questionnaire for global health status (QLQ-C30) and the supplemental 13-item lung cancer module (QLQ-LC13), focusing on a composite endpoint of cough, chest pain, and dyspnea.
Study results showed that at week 15, patients in the pembrolizumab group had experienced an increase in QLQ-C30 mean score of 6.9 points, whereas those in the chemotherapy group had experienced a decrease in QLQ-C30 mean score of 0.9 points (P = .002), Dr. Brahmer reported.
Additionally, patients in the pembrolizumab group had a longer time to deterioration in the QLQ-LC13 composite of cough, chest pain, and dyspnea, which was defined as a reduction in the score for at least 1 of these symptoms by at least 10 points and confirmed by a second reduction of that magnitude (HR = 0.66; P = .029).
Pembrolizumab-treated patients also had more favorable changes in scores on individual QLQ-C30 scales for functioning and symptoms and in QLQ-LC13 scores for specific symptoms. ■
Disclosure: Julie Renee Brahmer, MD, has received research support from Bristol-Myers Squibb, Medimmune/AstraZeneca, and Merck and is a consultant for Bristol-Myers Squibb (uncompensated), Celgene, Eli Lilly, and Merck, the sponsor of KEYNOTE-024.
1. Brahmer JR, Rodriguez-Abreu D, Robinson AG, et al: Health-related quality of life for pembrolizumab vs chemotherapy in advanced NSCLC with PD-L1 TPS ≥ 50%: Data from KEYNOTE-024. 2016 World Conference on Lung Cancer. Abstract PL04a.01. Presented December 7, 2016.
2. Reck M, Rodríguez-Abreu D, Robinson AG, et al: Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375:1823-1833, 2016.
“This was a very nice analysis using a well-validated group of instruments with high compliance. And this is something that is one of the bugbears of quality-of-life analyses—compliance to completion of the instruments,” commented invited discussant, Michael Boyer, MBBS, PhD, Chief Clinical Officer ...