Julie Brahmer, MD
Patients with non–small cell lung cancer (NSCLC) treated in the pembrolizumab (Keytruda) arm of the KEYNOTE-024 trial experienced improved quality of life (QoL) compared with patients who were treated with standard chemotherapy, according to new data from an exploratory analysis of the trial presented at the IASLC 17th World Conference on Lung Cancer in Vienna, Austria.
The prespecified exploratory patient-reported outcomes (PRO) analysis sought to determine if these positive results would translate into significant improvements in QoL for this patient population, an important metric in anti-cancer 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, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, 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 with 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
Along with the agent’s frontline approval, the FDA has also authorized an update to pembrolizumab’s label to include data from the KEYNOTE-010 trial, which looked at the PD-1 inhibitor in the second-line setting and beyond for patients with NSCLC and PD-L1 expression levels of ≥1% who have progressed on platinum-based chemotherapy and EGFR- or ALK-targeted therapy for individuals harboring those aberrations.
In the KEYNOTE-024 study, a total of 305 patients were randomized to either a treatment regimen of pembrolizumab at a dose of 200 mg every 3 weeks, or investigator’s choice of platinum-doublet chemotherapy, which most commonly included carboplatin plus pemetrexed (n = 67). 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).
The results of this analysis of KEYNOTE-024 showed that, across all treatment arms, PRO compliance was >90% at baseline and approximately 80% at week 15.
Least squares (LS) mean (95% CI) change from baseline to week 15 in QLQ-C30 global health status/QoL score was 6.95 (3.29 to 10.58) for pembrolizumab (n = 151) and -0.88 (-4.78 to 3.02) for standard chemotherapy (n = 148). The difference in LS means was 7.82 (95% CI, 2.85-12.79; nominal 2-sided P
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 (HR, 0.66; 95% CI, 0.44-0.97; nominal 2-sided P
Any-grade (73% vs 90%) and grade 3 to 5 (27% vs 53%) 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.
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