Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50

Abstract

Purpose: We report the first 5-year follow-up of any first-line phase III immunotherapy trial for non-small-cell lung cancer (NSCLC). KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738) is an open-label, randomized controlled trial of pembrolizumab compared with platinum-based chemotherapy in patients with previously untreated NSCLC with a programmed death ligand-1 (PD-L1) tumor proportion score of at least 50% and no sensitizing EGFR or ALK alterations. Previous analyses showed pembrolizumab significantly improved progression-free survival and overall survival (OS).

Methods: Eligible patients were randomly assigned (1:1) to pembrolizumab (200 mg once every 3 weeks for up to 35 cycles) or platinum-based chemotherapy. Patients in the chemotherapy group with progressive disease could cross over to pembrolizumab. The primary end point was progression-free survival; OS was a secondary end point.

Results: Three hundred five patients were randomly assigned: 154 to pembrolizumab and 151 to chemotherapy. Median (range) time from randomization to data cutoff (June 1, 2020) was 59.9 (55.1-68.4) months. Among patients initially assigned to chemotherapy, 99 received subsequent anti-PD-1 or PD-L1 therapy, representing a 66.0% effective crossover rate. Median OS was 26.3 months (95% CI, 18.3 to 40.4) for pembrolizumab and 13.4 months (9.4-18.3) for chemotherapy (hazard ratio, 0.62; 95% CI, 0.48 to 0.81). Kaplan-Meier estimates of the 5-year OS rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients received 35 cycles (ie, approximately 2 years) of pembrolizumab, 82.1% of whom were still alive at data cutoff (approximately 5 years). Toxicity did not increase with longer treatment exposure.

Conclusion: Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC with PD-L1 tumor proportion score of at least 50%.

FIG 1.

Disposition of patients. ^aNumber of patients who completed treatment, as reported by investigator. AE, adverse event; PD, progressive disease; PD-L1, programmed death ligand-1; TPS, tumor proportion score.

FIG 2.

Kaplan-Meier estimates of (A) OS and (B) PFS in the pembrolizumab group and the chemotherapy group. For each treatment group, the Kaplan-Meier method was used to estimate OS and PFS, with censoring of data for patients alive or lost to follow-up at the time of last contact for OS or without disease progression or death at last disease assessment without documented disease progression prior to initiation of second-line therapy for PFS. Tick marks indicate censoring times. HR, hazard ratio; NR, not reached; OS, overall survival; PFS, progression-free survival.

FIG 3.

Kaplan-Meier estimates of PFS2 for each treatment group, with censoring of data at the time of last contact for patients alive without receiving second-line therapy, stopping second-line therapy without disease progression, and not initiating third-line therapy. Tick marks indicate censoring times. HR, hazard ratio; PFS, progression-free survival.

FIG 4.

Treatment duration and time to response in (A) patients completing 35 cycles of pembrolizumab treatment and (B) patients who received a second course of pembrolizumab treatment. Light red bars indicate the first course of pembrolizumab treatment duration. Light teal bars indicate the (A) first course follow-up duration or (B) second course of treatment duration. Follow-up was defined as the time to progression or last nonprogression assessment by investigator. Response was assessed by RECIST v1.1 per investigator review. The maximum treatment duration for the second course was 17 cycles. ^aPatient developed a secondary malignancy. CR, complete response; NE, nonevaluable; PD, progressive disease; PR, partial response; SD, stable disease.