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Abstract
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. Whole-exome 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.

Affiliations

J B Lee 1, K H Kim 2, S Yoon 3, S Y Song 4, S S Lee 5, S Jo 6, H K Ahn 7, H J Kim 8, S J Choi 9, H Park 9, M H Hong 1, B C Cho 1, H I Yoon 10, S M Lim 11
1Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
2Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
3Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
4Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
5Department of Hematology-Oncology; Inje University Haeundae Paik Hospital, Busan, Republic of Korea.
6Department of Radiation Oncology, Inje University Haeundae Paik Hospital, Busan, Republic of Korea.
7Division of Medical Oncology and Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
8Department of Radiation Oncology, Gachon University Gil Medical Center, Incheon, Republic of Korea.
9Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
10Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: yhi0225@yuhs.ac.
11Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: limlove2008@yuhs.ac.