Health-Related Quality-of-Life Results of the KEYNOTE-598 Trial in Patients with Metastatic NSCLC with PD-L1 Tumor Proportion Score ≥50%

Primary analysis of the phase 3 KEYNOTE-598 study did not demonstrate improvements in overall survival and progression-free survival with pembrolizumab + ipilimumab compared with pembrolizumab + placebo in patients with previously untreated metastatic non–small-cell lung cancer (NSCLC) with PD-L1 tumor proportion score (TPS) ≥50%; however, incidence of treatment-related grade 3-5 adverse events (AEs), fatal AEs, and AEs leading to discontinuation were higher with dual immunotherapy. Results of prespecified patient-reported outcome (PRO) analyses from KEYNOTE-598 were presented at the 2021 ASCO meeting.

The KEYNOTE-598 trial randomized patients with previously untreated stage IV NSCLC with PD-L1 TPS ≥50% and without EGFR/ALK genomic alterations to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles + ipilimumab 1 mg/kg or pembrolizumab plus placebo every 6 weeks for up to 18 cycles. Health-related quality-of-life (QOL) measures, including the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30), Quality-of-Life Questionnaire-Lung Cancer 13 (QLQ-LC13), EuroQol 5 Dimension 5 Level (EQ-5D-5L), and NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) were administered at cycles 1 through 7, then every 3 cycles through cycle 19, and every 4 cycles until progressive disease or a maximum of 35 cycles. Secondary objectives of the KEYNOTE-598 trial were change from baseline in global health status (GHS)/QOL score from the QLQ-C30 and the time to true deterioration (TTD) in the composite end point of cough (LC13), chest pain (LC13), or dyspnea (C30). PROs were analyzed in all patients who completed ≥1 PRO assessments and received ≥1 doses of study treatment.

The PRO cohort included 280 patients in each of the 2 treatment groups; completion rates of PRO measures were similar in the 2 groups at baseline (~95%), week 18 (63%-70%%), week 36 (46%-54%), and week 54 (32%-40%). The mean QLQ-C30 GHS/QOL scores in the pembrolizumab + ipilimumab group and the pembrolizumab + placebo group were similar at baseline (62.8% and 64.2%) and week 18 (69.9% and 70.8%). Both treatment groups showed improvement in least squares (LS) mean (95% confidence interval [CI]) change from baseline to week 18 in GHS/QOL scores (pembrolizumab + ipilimumab: 3.7 [95% CI, 0.9-6.5]; pembrolizumab + placebo: 4.1 [95% CI, 1.4-6.9]), with no significant between-group difference (LS mean difference: −0.42 [95% CI, −4.0 to 3.1]; P = .82). Median TTD in composite of cough, chest pain, or dyspnea was not reached (NR; 95% CI, 13.0 months-NR) in the pembrolizumab + ipilimumab group versus 20.0 months (95% CI, 12.7-NR) in the pembrolizumab + placebo group (hazard ratio, 0.98; 95% CI, 0.74-1.30; P = .91).

Based on the results of the PRO analyses of the KEYNOTE-598 trial, there were no differences in health-related QOL or TTD in lung cancer symptoms between pembrolizumab + ipilimumab and pembrolizumab + placebo in patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥50%, indicating that addition of ipilimumab to pembrolizumab does not improve PRO outcomes in this setting.

Source: Sendur MN, et al. J Clin Oncol. 2021;39(suppl 15):Abstract 9038.