Julie Brahmer, MD
This prespecified exploratory patient-reported outcomes (PROs) analysis sought to determine if KEYNOTE-24’s positive results would translate into significant improvements in QOL for this patient population, an important metric in anticancer therapy as it relates to treatment in the first-line setting.
“Pembrolizumab was associated with a clinically meaningful improvement in healthcare QOL and in the time to deterioration for cough, dyspnea, and chest pain, compared with platinum-based chemotherapy,” Julie Brahmer, MD, associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, said in a statement.
In the KEYNOTE-024 trial, single-agent pembrolizumab reduced the risk of death by 40% and improved progression-free survival (PFS) by 4.3 months compared with doublet chemotherapy for untreated patients with advanced NSCLC who had PD-L1 expression on ≥50% of cells. These results have been hailed as practice-changing, and they have since led to the FDA approval of pembrolizumab as a frontline treatment for these patients with PD-L1 tumor expression based on an FDA-approved test, who do not harbor EGFR or ALK aberrations.
In the KEYNOTE-024 study, 305 patients were randomized to a treatment regimen of either pembrolizumab (200 mg every 3 weeks), or investigator’s choice of platinum-doublet chemotherapy, which most commonly included carboplatin plus pemetrexed. Forty-six patients in the chemotherapy arm went on to receive maintenance therapy with pemetrexed, and an additional 66 patients (43.7%) crossed over to the pembrolizumab arm following progression.
The PRO endpoints of the exploratory analysis included change from baseline to week 15 using the QLQ-C30 global health status/QOL score, as well as time to deterioration with the QLQ-LC13 composite score of cough, chest pain, and dyspnea.
PROs were analyzed for all patients who received the study treatment and completed >1 PRO instrument (n = 299). Across all treatment arms, PRO compliance was >90% at baseline and approximately 80% at week 15.
The proportion of improved global health status/QOL score at week 15, defined as a 10-point or greater change from baseline, was 40% for patients treated with pembrolizumab and 26.5% for patients treated with chemotherapy.
In the pembrolizumab treatment arm of the study, fewer patients experienced deterioration in the QLQ-LC13 composite of cough, dyspnea, and chest pain (30% vs 39%). Plus, the time to deterioration was prolonged with the PD-1 inhibitor. Treatment-related adverse events were less frequent in patients treated with pembrolizumab.
“Combined with the superior PFS and overall survival rate of patients on pembrolizumab and manageable safety profile, these data suggest pembrolizumab may be a new standard of care for first-line treatment of PD-L1–expressing advanced NSCLC,” said Brahmer.
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. Presented at: IASLC 17th World Conference on Lung Cancer; December 4-7, 2016; Vienna, Austria.