Lung cancer (Amsterdam, Netherlands) · 2025
Real-world outcomes of second-line carboplatin plus pemetrexed after first-line osimertinib in EGFR-mutant advanced NSCLC: An international multicentre cohort study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Gomez-Randulfe Igor, Monaca Federico, Cantale Ornella, Reale Maria Lucia, Mrak Loredana, Zullo Lodovica, Diaz Sofia Silva, Bueno Marta Zaragoza, Maridueña Moreno Marya Alejandra, Davis Charlotte, Cox Samantha, Lee Daniel, Shah Riyaz, Geldart Tom, Baena Javier, Benitez Jose Carlos, Rosario Garcia Campelo M A, Remon Jordi, Planchard David, Galetta Domenico, Tiseo Marcello, Cortinovis Diego, Metro Giulio, Bria Emilio, Passiglia Francesco, Novello Silvia, Califano Raffaele
Аннотация
BACKGROUND: First-line osimertinib is one of the standards of care for EGFR-mutant advanced non-small cell lung cancer (NSCLC), but most patients eventually progress. After progression, carboplatin plus pemetrexed remains the most widely used second-line therapy, yet robust real-world data in this setting are scarce.
METHODS: We conducted a retrospective multicentre cohort study from four European countries in patients with EGFR-mutant advanced NSCLC who received second-line carboplatin plus pemetrexed following osimertinib. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate (ORR), safety, and exploratory analyses of associations between baseline factors and outcomes.
RESULTS: We identified a total of 252 patients. Median PFS and OS were 5.3 months (95 % CI 4.7-5.9) and 9.6 months (95 % CI 8.2-11.1), respectively. The ORR was 40.7 %, with grade ≥ 3 adverse events reported in 19.3 % of patients. ECOG ≥ 2 and liver metastases independently predicted worse OS; ECOG ≥ 2 and a history of smoking were associated with shorter PFS. Early progression on osimertinib (<18 months) correlated with shorter OS (8.3 vs 14.7 months; HR 1.66, P = 0.005). Neither the timing between osimertinib discontinuation and chemotherapy initiation nor EGFR mutation subtype influenced efficacy.
CONCLUSIONS: In real-world European practice, second-line carboplatin plus pemetrexed provides modest benefit post-osimertinib, with outcomes strongly influenced by ECOG status, metastatic burden, and prior osimertinib duration. Despite a clinically diverse cohort, outcomes were consistent with historical reports. These data help define benchmarks for future trials and underscore the need for personalised sequencing strategies, particularly in high-risk subgroups.
METHODS: We conducted a retrospective multicentre cohort study from four European countries in patients with EGFR-mutant advanced NSCLC who received second-line carboplatin plus pemetrexed following osimertinib. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate (ORR), safety, and exploratory analyses of associations between baseline factors and outcomes.
RESULTS: We identified a total of 252 patients. Median PFS and OS were 5.3 months (95 % CI 4.7-5.9) and 9.6 months (95 % CI 8.2-11.1), respectively. The ORR was 40.7 %, with grade ≥ 3 adverse events reported in 19.3 % of patients. ECOG ≥ 2 and liver metastases independently predicted worse OS; ECOG ≥ 2 and a history of smoking were associated with shorter PFS. Early progression on osimertinib (<18 months) correlated with shorter OS (8.3 vs 14.7 months; HR 1.66, P = 0.005). Neither the timing between osimertinib discontinuation and chemotherapy initiation nor EGFR mutation subtype influenced efficacy.
CONCLUSIONS: In real-world European practice, second-line carboplatin plus pemetrexed provides modest benefit post-osimertinib, with outcomes strongly influenced by ECOG status, metastatic burden, and prior osimertinib duration. Despite a clinically diverse cohort, outcomes were consistent with historical reports. These data help define benchmarks for future trials and underscore the need for personalised sequencing strategies, particularly in high-risk subgroups.