In a meta-analysis reported in JAMA Oncology, Di Federico et al found that the addition of first-line platinum-based chemotherapy to PD-1/-L1 inhibition was associated with improved outcomes in patients with advanced non–small cell lung cancer (NSCLC) with high PD-L1 expression.
Study Details
The analysis included data from phase III trials (reported before August 2025) evaluating PD-1/-L1 inhibitor monotherapy with or without platinum-based chemotherapy vs chemotherapy alone in patients with untreated advanced disease and high PD-L1 expression (50% or higher). The main outcome measures were overall survival (primary) and progression-free survival.
Key Findings
Among 24 eligible trials including 5,546 patients with PD-L1–high NSCLC, 16 evaluated chemoimmunotherapy and 8 evaluated PD-1/-L1 inhibitor monotherapy.
Compared with patients receiving chemotherapy alone, those receiving chemoimmunotherapy had significantly improved overall survival (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.56–0.72, P < .001) and progression-free survival (HR = 0.44, 95% CI = 0.39–0.49, P < .001). Compared with chemotherapy alone, patients receiving PD-1/-L1 inhibitor monotherapy had significantly improved overall survival (HR = 0.74, 95% CI = 0.69–0.80, P < .001) and progression-free survival (HR = 0.70, 95% CI = 0.65–0.76, P < .001).
Tests for subgroup differences indicated increased benefit with chemoimmunotherapy vs PD-1/-L1 inhibitor monotherapy for overall survival (χ12 = 4.1; P = .04; I2 = 75.8%) and progression-free survival (χ12 = 48.1; P < .001; I2 = 97.9%); this finding was consistent with those of meta-regression analyses for overall survival (HR = 0.85, 95% CI = 0.72–1.00, P = .048) and progression-free survival (HR = 0.61, 95% CI = 0.50–0.75, P < .001) as well as network meta-analyses for overall survival (HR = 0.85, 95% CI = 0.73–0.99) and progression-free survival (HR = 0.61, 95% CI = 0.50–0.75).
Further, reconstructed individual patient data analysis showed a median overall survival of 29.2 months (95% CI = 25.2–35.4 months) among 704 patients who received chemoimmunotherapy vs 19.8 months (95% CI = 18.3–21.7 months) among 1,706 patients receiving PD-1/-L1 inhibitor monotherapy (HR = 0.74, 95% CI = 0.66–0.82, P < .001). Corresponding median progression-free survival was 11.3 months (95% CI = 10.3–13.5 months) vs 6.8 months (95% CI = 6.2–7.1 months; HR = 0.67, 95% CI = 0.60–0.75, P < .001).
The investigators concluded: “In this meta-analysis of phase III [randomized controlled trials], chemoimmunotherapy was associated with significantly improved [overall survival and progression-free survival] compared with PD-1/-L1 inhibitor monotherapy in patients with advanced NSCLC and high PD-L1 expression. Prospective trials are needed to confirm these findings.”
Biagio Ricciuti, MD, PhD, of Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, is the corresponding author for the JAMA Oncology article.
DISCLOSURE: The study was supported by the European Union–NextGenerationEU through the Italian Ministry of University and Research. For full disclosures of the study authors, visit jamanetwork.com.
