Introduction: EGFR tyrosine kinase inhibitors, including osimertinib, generally exhibit lower efficacy in patients with the L858R-mutant NSCLC compared with those with exon 19 deletion (del19). Ramucirumab (RAM) plus erlotinib (ERL), however, has demonstrated comparable efficacy in patients with either del19 or L858R mutations. Despite these findings, the real-world clinical efficacy of the RAM plus ERL combination therapy for the L858R-mutation NSCLC remains unclear, particularly in patients with central nervous system metastases.
Methods: The authors performed a retrospective multicenter cohort study for 168 patients with L858R-mutant NSCLC treated with RAM plus ERL as a first-line treatment between November 2020 and August 2023.
Results: The median time to treatment failure was 12.2 months (95% confidence interval [CI]: 9.5-15.5), and the median progression-free survival was 17.4 months (95% CI: 14.8-24.8). The median overall survival was 35.6 months (95% CI: 30.3-not calculable), resulting in 77.8% at a 2-year survival rate. The objective response rate was 75.0%, and the disease control rate was 88.7%. Among the cohort, 43 patients (26%) had central nervous system metastasis, with a median progression-free survival of 15.1 months (95% CI: 8.2-19.9). The most common adverse events were dermatitis acneiform (71%), paronychia (43%), and diarrhea (39%). Grade more than or equal to 3 adverse events occurred in 42% of patients.
Conclusions: In real-world settings, RAM plus ERL demonstrated favorable efficacy in patients with L858R-mutant NSCLC and manageable toxicity.
Keywords: EGFR-TKI; Erlotinib; L858R; Non–small cell lung cancer; Ramucirumab.
© 2026 The Authors.