Lazertinib plus pemetrexed and carboplatin in patients with EGFR-mutant advanced non-small cell lung cancer after progression on lazertinib.
Min Hee Hong, Byoung Yong Shim, Chang Gon Kim et al.
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In 30 seconds
The multicenter, single-arm phase II LUCAS study evaluated continued lazertinib with pemetrexed-carboplatin, followed by lazertinib and pemetrexed maintenance, in patients with advanced EGFR-mutant NSCLC progressing on lazertinib. Among 81 response-evaluable patients, median progression-free survival 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, objective response rate was 36.0% (95% CI: 26.0-47.1), and median overall survival was 15.9 months (95% CI: 12.4-20.0).
Key findings
- 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) among 81 response-evaluable patients.
- ORR was 36.0% (95% CI: 26.0-47.1), and median OS was 15.9 months (95% CI: 12.4-20.0).
- Among 36 patients with 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; no new safety signals were reported.
Why it matters
The findings suggest that maintaining EGFR inhibition alongside platinum-pemetrexed chemotherapy can have systemic and intracranial activity after progression on lazertinib. This is clinically relevant because treatment options after progression on third-generation EGFR-TKIs remain suboptimal. However, the observed outcomes do not establish how much benefit comes from continuing lazertinib rather than chemotherapy alone.
What to keep in mind
The study was single-arm, so it cannot establish the incremental benefit of continuing lazertinib; the authors state that randomized evaluation is required.