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

Author(s): Ross A. Soo, MBBS, PhD1; Byoung Chul Cho, MD, PhD2; Joo-Hang Kim, MD3; Myung-Ju Ahn, MD, PhD4; Ki Hyeong Lee, MD5; Anastasia Zimina, MD6; Sergey Orlov, MD7; Igor Bondarenko, MD, PhD8; Yun-Gyoo Lee, MD9; Yueh Ni Lim, MD10; Sung Sook Lee, MD11; Kyung-Hee Lee, MD, PhD12; Yong Kek Pang, MD13; Chin Heng Fong, MD14; Jin Hyoung Kang, MD15; Chun Sen Lim, MD16; Pongwut Danchaivijitr, MD17; Saadettin Kilickap, MD18; James Chih-Hsin Yang, MD, PhD19; Cagatay Arslan, MD20; Hana Lee, MS21; Seong Nam Park, MPH21; Irfan Cicin, MD22
Source: https://doi.org/10.1016/j.jtho.2023.08.017
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Lazertinib, third generation EGFR inhibitor, has good activity in patients with brain mets promising…

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.

Author Affiliations

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

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