Immunotherapy Agent Improved Quality of Life in Lung Cancer Study

There was a quality of life (QoL) improvement for patients with non-small cell lung cancer (NSCLC) who were treated with the Keytruda (pembrolizumab) arm of the KEYNOTE-024 compared to those who had standard chemotherapy, according to new data from 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, M.D., 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 Keytruda reduced the risk of death by 40 percent 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 percent or more 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.

Along with the agent’s frontline approval, the FDA has also authorized an update to Keytruda’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 percent or higher 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 Keytruda at a dose of 200 mg every three weeks, or investigator’s choice of platinum-doublet chemotherapy, which most commonly included carboplatin plus pemetrexed (67 patients). Forty-six patients in the chemotherapy arm went on to receive maintenance therapy with pemetrexed, and an additional 66 patients (43.7 percent) crossed over to the Keytruda 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 at least 1 PRO instrument (299 patients).

The results of this analysis of KEYNOTE-024 showed that, across all treatment arms, PRO compliance was more than 90 percent at baseline and approximately 80 percent at week 15.

Least squares (LS) mean change from baseline to week 15 in QLQ-C30 global health status/QoL score was 6.95 (3.29 to 10.58) for Keytruda (151 patients) and -0.88 (-4.78 to 3.02) for standard chemotherapy (148 patients). The difference in LS means was 7.82.

The proportion of improved global health status/QoL score at week 15, defined as a 10-point or greater change from baseline, was 40 percent for patients treated with Keytruda and 26.5 percent for patients treated with chemotherapy.

In the Keytruda treatment arm of the study, fewer patients experienced deterioration in the QLQ-LC13 composite of cough, dyspnea, and chest pain (30 percent vs 39 percent). Plus, the time to deterioration was prolonged with the PD-1 inhibitor.

Any-grade (73 percent vs 90 percent) and grade 3 to 5 (27 percent vs 53 percent) treatment-related adverse events were less frequent in patients treated with Keytruda.

“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 percent: Data from KEYNOTE-024. Presented at: IASLC 17^th World Conference on Lung Cancer; December 4-7, 2016; Vienna, Austria.