Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301

Cho BC 1 , Ahn MJ 2 , Kang JH 3 , Soo RA 4 , Reungwetwattana T 5 , Yang JC 6 Show all authors , Cicin I 7 , Kim DW 8 , Wu YL 9 , Lu S 10 , Lee KH 11 , Pang YK 12 , Zimina A 13 , Fong CH 14 , Poddubskaya E 15 , Sezer A 16 , How SH 17 , Danchaivijitr P 18 , Kim Y 19 , Lim Y 19 , An T 19 , Lee H 19 , Byun HM 19 , Zaric B 20

Affiliations 

  • 1 Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
  • 2 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  • 3 Division of Medical Oncology, Department of Internal Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea
  • 4 National University Hospital, Singapore, Singapore
  • 5 Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  • 6 National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan
  • 7 Department of Medical Oncology, Trakya University Medical Center, Edirne, Turkey
  • 8 Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
  • 9 Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
  • 10 Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China
  • 11 Internal Medicine Department, Chungbuk National University Hospital, Cheongju, Republic of Korea
  • 12 Department of Medicine, Faculty of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia
  • 13 Department of Oncology, Omsk Clinical Oncological Dispensary, Omsk, Russian Federation
  • 14 Department of Radiotherapy and Oncology, Hospital Pulau Pinang, Penang, Malaysia
  • 15 Personalized Oncology Department, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
  • 16 Adana Baskent Practice and Research Hospital, Adana, Turkey
  • 17 Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia
  • 18 Siriraj Hospital, Bangkok, Thailand
  • 19 Yuhan Corporation, Seoul, Republic of Korea
  • 20 Faculty of Medicine, Institute for Pulmonary Diseases of Vojvodina, University of Novi Sad, Novi Sad, Serbia
J Clin Oncol, 2023 Sep 10;41(26):4208-4217.
PMID: 37379502 DOI: 10.1200/JCO.23.00515

Abstract

PURPOSE: Lazertinib is a potent, CNS-penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This global, phase III study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Patients were 18 years and older with no previous systemic anticancer therapy. Neurologically stable patients with CNS metastases were allowed. Patients were randomly assigned 1:1 to lazertinib 240 mg once daily orally or gefitinib 250 mg once daily orally, stratified by mutation status and race. The primary end point was investigator-assessed progression-free survival (PFS) by RECIST v1.1.

RESULTS: Overall, 393 patients received double-blind study treatment across 96 sites in 13 countries. Median PFS was significantly longer with lazertinib than with gefitinib (20.6 v 9.7 months; hazard ratio [HR], 0.45; 95% CI, 0.34 to 0.58; P < .001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups. The objective response rate was 76% in both groups (odds ratio, 0.99; 95% CI, 0.62 to 1.59). Median duration of response was 19.4 months (95% CI, 16.6 to 24.9) with lazertinib versus 8.3 months (95% CI, 6.9 to 10.9) with gefitinib. Overall survival data were immature at the interim analysis (29% maturity). The 18-month survival rate was 80% with lazertinib and 72% with gefitinib (HR, 0.74; 95% CI, 0.51 to 1.08; P = .116). Observed safety of both treatments was consistent with their previously reported safety profiles.

CONCLUSION: Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.

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

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