Safety, Efficiency of Pembrolizumab Monotherapy in Geriatric PD-L1+ NSCLC


A pooled analysis of safety, efficacy of pembrolizumab in patients 75+ years of age with PD-L1+ NSCLC

Scientists from around the globe recently came together to conduct a pooled analysis of safety and efficacy of the programmed death 1 inhibitor, pembrolizumab in patients 75 years of age or older diagnosed with advanced non–small-cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1)‒positive tumors. The analysis was based on the KEYNOTE-010, -024, and -042 studies.

The researchers concluded that pembrolizumab improved survival when compared with chemotherapy for PD-L1‒positive advanced NSCLC. They observed no unexpected toxicity from pembrolizumab in patients 75 year of age or older, and outcomes for this group were similar to those in the overall study population.

Most lung cancer diagnoses occur in elderly patients, and yet this population is underrepresented in clinical trials, making this analysis important for the majority of NSCLC patients. The geriatric population has a greater number of tolerability issues due to impaired reduced cognitive, cardiac or renal function, or other comorbidities. Other studies have noted that side effects and treatment discontinuation rates are higher among advanced NSCLC patients who are 70 years of age or older and undergoing platinum-based chemotherapy.

The retrospective and exploratory pooled analyses examined patients ages 18 years or older from the KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894) studies, who had advanced NSCLC with PD-L1–positive tumors.

Patients in KEYNOTE-010 were randomized to either pembrolizumab-2mg/kg or 10 mg/kg-every 3 weeks (Q3W), or to docetaxel as second-line or later therapy. Patients in KEYNOTE-024 and KEYNOTE-042 were randomized to either first-line pembrolizumab 200 mg Q3W, or platinum-based chemotherapy. Researchers detailed safety data and estimated overall survival (OS) by the Kaplan-Meier method.

In all, 264 elderly patients with PD-L1–positive tumors (PD-L1 tumor proportion score [TPS] ≥1%) were analyzed. Of this total, 132 had PD-L1 TPS ≥ 50%. Pembrolizumab improved OS in patients 75 years of age or older who had PD-L1 TPS ≥ 1% (hazard ratio [HR], 0.76 [95% CI, 0.56–1.02]) and PD-L1 TPS ≥ 50% (HR, 0.40 [95% CI, 0.25–0.64]). Used a first-line therapy, pembrolizumab also improved OS among elderly patients with PD-L1 TPS ≥ 50% (from KEYNOTE-024 and KEYNOTE-042) when compared with chemotherapy (HR, 0.41 [95% CI, 0.23‒0.73]). The extent of benefit with pembrolizumab increased concurrent with rising levels of PD-L1 expression.There appeared to be fewer treatment-related adverse events (AEs) associated with pembrolizumab versus chemotherapy used in the geriatric population (overall, 68.5% vs 94.3%; grade ≥3, 24.2% vs 61.0%). Both immune-mediated AEs as well as infusion reactions were more likely with a pembrolizumab regime than with those using chemotherapy (overall, 24.8% vs 6.7%; grade 3‒4: 9.4% vs 0%; no grade 5 events).

Compared with chemotherapy, pembrolizumab had a greater safety profile in elderly patients with advanced NSCLC and PD-L1‒positive tumors, and resulted in a more favorable prognosis. Furthermore, older age was not associated with increased toxicity from pembrolizumab therapy than was seen in younger populations.

Related Videos
Video 4 - "Frontline Treatment for EGFR-Mutated Lung Cancer"
Video 3 - "NGS Testing Challenges and Considerations in NSCLC"
Related Content