Tumor Response Dynamics During First-Line Pembrolizumab Therapy in Patients With Advanced Non–Small-Cell Lung Cancer

Abstract

PURPOSE The objectives of the study were to characterize the tumor burden dynamics on serial computed tomography scans in patients with advanced non–small-cell lung cancer treated with first-line pembrolizumab and to identify imaging markers for prolonged overall survival (OS). MATERIALS AND METHODS Eighty-eight patients treated with first-line pembrolizumab monotherapy were evaluated on serial computed tomography scans to characterize their quantitative tumor burden during therapy. Tumor burden dynamics were studied for the association with OS. RESULTS The overall response rate was 42% (37/88), with the median tumor burden changes at the best overall response of −18.3% (range, −100.0% to +103.6%). Response rates were higher in men than in women ( P = .05) and in patients with higher programmed cell death ligand-1 expression levels ( P = .02). Tumor burden stayed below the baseline burden throughout therapy in 55 patients (63%). In an 8-week landmark analysis, patients with tumor burden below the baseline burden during the first 8 weeks of therapy had longer OS compared with patients who had ≥ 0% increase (median OS, 30.7 v 16.2 months; hazard ratio [HR] = 0.44; P = .01). In the extended Cox models, patients whose tumor burden stayed below the baseline burden throughout therapy had significantly reduced hazards of death (HR = 0.41, P = .003, univariate; HR = 0.35, P = .02, multivariate). Only one patient (1.1%) experienced pseudoprogression with initial tumor increase and subsequent tumor regression. CONCLUSION In patients with advanced non–small-cell lung cancer treated with first-line single-agent pembrolizumab, tumor burden reduction below the baseline burden during therapy was an independent marker for prolonged OS, which may serve as a practical guide for treatment decisions.