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Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis

Soo RA 1 , Cho BC 2 , Kim JH 3 , Ahn MJ 4 , Lee KH 5 , Zimina A 6 Show all authors , Orlov S 7 , Bondarenko I 8 , Lee YG 9 , Lim YN 10 , Lee SS 11 , Lee KH 12 , Pang YK 13 , Fong CH 14 , Kang JH 15 , Lim CS 16 , Danchaivijitr P 17 , Kilickap S 18 , Yang JC 19 , Arslan C 20 , Lee H 21 , Park SN 21 , Cicin I 22

Affiliations 

  • 1 Department of Haematology-Oncology, National University Cancer Institute, Singapore
  • 2 Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
  • 3 CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
  • 4 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  • 5 Division of Medical Oncology, Department of Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea
  • 6 State Budgetary Healthcare Institution of Omsk Region, Omsk, Russia
  • 7 Pavlov State Medical University, Ulitsa L'va Tolstogo, St. Petersburg, Russia
  • 8 Oncology and Medical Radiology Department, Dnipropetrovsk Medical Academy, Dnipro, Ukraine
  • 9 Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  • 10 Hospital Umum Sarawak, Jalan Hospital, Kuching, Malaysia
  • 11 Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
  • 12 Division of Hematology/Oncology, Department of Internal Medicine, Yeungnam University Medical Center, Daegu, Republic of Korea
  • 13 University Malaya Medical Centre, University of Malaya, Petaling Jaya, Malaysia
  • 14 Hospital Pulau Pinang, Pulau Pinang, Malaysia
  • 15 Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea
  • 16 Oncology Department, Hospital Sultan Ismail, Jalan Mutiara Emas Utama, Johor, Malaysia
  • 17 Division of Medical Oncology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • 18 Department of Medical Oncology, İstinye University Faculty of Medicine, Liv Hospital Ankara, Ankara, Turkey
  • 19 National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei City, Taiwan
  • 20 Department of Medical Oncology, Izmir University of Economics Medical Point Hospital, İzmir, Turkey
  • 21 Yuhan Corporation, Seoul, Republic of Korea
  • 22 Department of Medical Oncology, Trakya University Medical Center, Edirne, Turkey. Electronic address: irfancicin@hotmail.com
J Thorac Oncol, 2023 Dec;18(12):1756-1766.
PMID: 37865896 DOI: 10.1016/j.jtho.2023.08.017

Abstract

INTRODUCTION: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases.

METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.

RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.

CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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