European journal of cancer (Oxford, England : 1990) · 2026
Lazertinib plus pemetrexed and carboplatin in patients with EGFR-mutant advanced non-small cell lung cancer after progression on lazertinib.
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Hong Min Hee, Shim Byoung Yong, Kim Chang Gon, Kim Young Saing, Lee Seoyoung, Lee Youngjoo, Ahn Beung-Chul, Ahn Myung-Ju, Ahn Jin Seok, Park Sehhoon, Yeo Ja Hyun, Hong Sook Hee, Jang In Hwan, Lee Ki Hyeong, Kim Hye Ryun
Аннотация
BACKGROUND: Therapeutic strategies after progression on third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) remain suboptimal in EGFR-mutant non-small cell lung cancer (NSCLC). We investigated whether continuing EGFR inhibition with lazertinib combined with platinum-pemetrexed chemotherapy could extend clinical benefit after progression on prior lazertinib.
METHODS: In the multicenter, single-arm, phase II LUCAS study (NCT05786430), patients with advanced EGFR-mutant NSCLC who had progressed on lazertinib received lazertinib 240 mg daily plus pemetrexed-carboplatin for four cycles, followed by maintenance lazertinib and pemetrexed. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), intracranial PFS, safety, and exploratory ctDNA analyses.
RESULTS: Of 86 patients, 46.5% had a history of brain metastases. Among 81 response-evaluable patients, median PFS was 9.5 months (95% CI: 6.3-9.6; one-sided p = 0.017 against a null median of 6.0 months). In the safety population, median OS was 15.9 months (95% CI: 12.4-20.0) and ORR was 36.0% (95% CI: 26.0-47.1). Outcomes were similar irrespective of prior lazertinib line or EGFR subtype. Baseline ctDNA-detected EGFR amplification was associated with inferior survival. Among 36 patients with radiologically evident baseline brain metastases, median intracranial PFS was 9.9 months (95% CI: 7.8-16.4) with infrequent isolated intracranial progression. Grade ≥ 3 adverse events occurred in 69.8%, predominantly hematologic, without new safety signals.
CONCLUSIONS: Continuation of lazertinib with platinum-pemetrexed chemotherapy after progression on prior lazertinib was associated with meaningful systemic and intracranial activity and manageable toxicity. Randomized evaluation is required to establish the incremental benefit of lazertinib continuation.
METHODS: In the multicenter, single-arm, phase II LUCAS study (NCT05786430), patients with advanced EGFR-mutant NSCLC who had progressed on lazertinib received lazertinib 240 mg daily plus pemetrexed-carboplatin for four cycles, followed by maintenance lazertinib and pemetrexed. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), intracranial PFS, safety, and exploratory ctDNA analyses.
RESULTS: Of 86 patients, 46.5% had a history of brain metastases. Among 81 response-evaluable patients, median PFS was 9.5 months (95% CI: 6.3-9.6; one-sided p = 0.017 against a null median of 6.0 months). In the safety population, median OS was 15.9 months (95% CI: 12.4-20.0) and ORR was 36.0% (95% CI: 26.0-47.1). Outcomes were similar irrespective of prior lazertinib line or EGFR subtype. Baseline ctDNA-detected EGFR amplification was associated with inferior survival. Among 36 patients with radiologically evident baseline brain metastases, median intracranial PFS was 9.9 months (95% CI: 7.8-16.4) with infrequent isolated intracranial progression. Grade ≥ 3 adverse events occurred in 69.8%, predominantly hematologic, without new safety signals.
CONCLUSIONS: Continuation of lazertinib with platinum-pemetrexed chemotherapy after progression on prior lazertinib was associated with meaningful systemic and intracranial activity and manageable toxicity. Randomized evaluation is required to establish the incremental benefit of lazertinib continuation.