Lazertinib with stereotactic body radiotherapy in oligometastatic EGFR-mutant non-small-cell lung cancer

초록

Background: Lazertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that demonstrated progression-free survival (PFS) benefit in treatment-naive, EGFR-mutant advanced non-small-cell lung cancer (NSCLC) as a single agent and in combination with amivantamab. Here, we report the clinical efficacy and safety profile of lazertinib plus stereotactic body radiotherapy (SBRT) in treatment-naive, EGFR-mutant oligometastatic NSCLC. Patients and methods: ABLATE is a phase II, multicenter, randomized, non-comparative study that included patients harboring activating EGFR mutations (ex19del or L858R) with synchronous oligometastatic disease (metastatic lesion <= 5). Patients received oral lazertinib 240 mg as monotherapy or in combination with SBRT, which was given immediately or 8 weeks after initiation of lazertinib. The primary endpoint was investigator-assessed PFS of lazertinib plus SBRT. Results: A total of 67 patients were enrolled in the study (n = 34, lazertinib; n = 33, lazertinib plus SBRT). At a median follow-up duration of 23.1 months (range 7.1-34.1 months), the median PFS was 34.0 months [90% confidence interval (CI) 19.2 months-not reached (NR)] and objective response rate (ORR) was 58% (95% CI 40.7% to 74.4%) for the lazertinib plus SBRT group. In lazertinib monotherapy, the median duration of follow-up was 22.4 months (range 3.7-33.5 months), the median PFS was 24.8 months (90% CI 15.7 months-NR), and ORR was 68% (95% CI 51.9% to 83.4%). SBRT led to local treatment effect with 92% (n = 12/14) progressing to new sites at progression. No new safety signals were seen with the addition of SBRT, and no grade >= 3 radiation pneumonitis was seen. Wholeexome sequencing of baseline tumor samples revealed that TP53 (64%), CRLF2 (43%), and P2RY9 (43%) were the most common mutations in patients treated with lazertinib plus SBRT. Conclusion: In treatment-naive, EGFR-mutant oligometastatic NSCLC, adding upfront SBRT to lazertinib is a viable therapeutic option with a manageable safety profile.

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