Lazertinib versus Gefitinib as First-Line Treatment for EGFR-Mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.
Abstract
Purpose This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.
참고문헌 (31)
- Kang MJ, "Cancer statistics in Korea : incidence, mortality, survival, and prevalence in 2019", Cancer Res Treat, 54, pp.330~344 (2022)
- Lee JG, "Recent trends of lung cancer in Korea", Tuberc Respir Dis, 84, pp.89~95 (2021)
- "Cancer inci dent cases and incidence rates (1999-2020)" (2023)[URL]
- Gazdar AF, "Activating and resistance mutations of EGFR in non-small-cell lung cancer : role in clinical response to EGFR tyrosine kinase inhibitors", Oncogene, 28(Suppl 1), pp.S24~S31 (2009)
- Midha A, "EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology : a systematic review and global map by ethnicity(mutMapII)", Am J Cancer Res, 5, pp.2892~2911 (2015)
- Maemondo M, "Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR", N Engl J Med, 362, pp.23808~ (2010)
- Wu YL, "Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer har bouring EGFR mutations(LUX-Lung 6) : an open-label, ran domised phase 3 trial", Lancet Oncol, 15, pp.213~222 (2014)
- Zhou C, "Erlo tinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer(OPTIMAL, CTONG-0802) : a multicentre, open-label, randomised, phase 3 study", Lancet Oncol, 12, pp.735~742 (2011)
- Westover D, "Mechanisms of acquired resistance to first-and second-gen eration EGFR tyrosine kinase inhibitors", Ann Oncol, 29, pp.i10~i19 (2018)
- Remon J, "Brain metastases in oncogene-addicted non small cell lung cancer patients : incidence and treatment", Front Oncol, 8, pp.88~ (2018)
- Rangachari D, "Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers", Lung Cancer, 88, pp.108~111 (2015)
- Nakagawa K, "RELAY subgroup analyses by EGFR Ex19del and Ex21L858R mutations for ramucirumab plus erlotinib in metastatic non-small cell lung cancer", Clin Cancer Res, 27, pp.5258~5271 (2021)
- Sheng M, "Com parison of clinical outcomes of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations after tyrosine kinase inhibitors treatment : a meta-analysis", Eur J Clin Pharmacol, 72, pp.1~11 (2016)
- Soria JC, "Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer", N Engl J Med, 378, pp.113~125 (2018)
- "LEC LAZA (lazertinib): Republic of Korea prescribing information" (2021)[URL]
- Yun J, "YH25448, an irreversible EGFR-TKI with potent intracranial activity in EGFR mutant non-small cell lung cancer", Clin Can cer Res, 25, pp.2575~2587 (2019)
- Ahn MJ, "Lazertinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer : results from the dose escalation and dose expansion parts of a first-in-human, open-label, multicentre, phase 1-2 study", Lancet Oncol, 20, pp.1681~1690 (2019)
- Cho BC, "A phase 1", 2 study of lazertinib 240 mg in patients with advanced EGFR T790M-positive NSCLC after previous EGFR tyrosine kinase inhibitors, 2022, pp.17, 558~567
- Cho BC, "Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non-small cell lung cancer : results from LASER301", J Clin Oncol, 41, pp.4208~4217 (2023)
- Cho BC, "EP08. 02-025 lazertinib as a frontline treatment in patients with EGFR mutant advanced non-small cell lung cancer : results from the phase I", II trial, 2022, pp.17(9Suppl), 408~409
- Ohe Y, "Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for EGFRm advanced NSCLC : FLAURA Japanese subset", Jpn J Clin Oncol, 49, pp.29~36 (2019)
- Cho BC, "Osimertinib versus stand ard of care EGFR TKI as first-line treatment in patients with EGFRm advanced NSCLC : FLAURA Asian subset", J Thorac Oncol, 14, pp.99~106 (2019)
- Togashi Y, "Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer", Cancer Chemother Pharmacol, 70, pp.399~405 (2012)
- Heon S, "Development of central nervous system metasta ses in patients with advanced non-small cell lung cancer and somatic EGFR mutations treated with gefitinib or erlotinib", Clin Cancer Res, 16, pp.5873~5882 (2010)
- Jung HA, "Totality outcome of afatinib sequential treatment in patients with EGFR mutation-positive non-small cell lung cancer in South Korea(TOAST) : Korean Cancer Study Group(KCSG)LU-19-22", Transl Lung Cancer Res, 11, pp.1369~1379 (2022)
- Yoon HY, "Clinical significance of EGFR mutation types in lung adenocarcino ma : a multi-centre Korean study", PLoS One, 15, pp.e0228925~ (2020)
- Choi YW, "Does the efficacy of epidermal growth fac tor receptor(EGFR)tyrosine kinase inhibitor differ according to the type of EGFR mutation in non-small cell lung cancer?", Korean J Intern Med, 32, pp.422~428 (2017)
- Mulloy R, "Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib", Cancer Res, 67, pp.2325~2330 (2007)
- Carey KD, "Kinetic analysis of epidermal growth factor receptor somatic mutant proteins shows increased sensitivity to the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib", Cancer Res, 66, pp.8163~8171 (2006)
- Jang SB, "Car diac safety assessment of lazertinib : findings from patients with EGFR mutation-positive advanced NSCLC and preclini cal studies", JTO Clin Res Rep, 2, pp.100224~ (2021)
- Batson S, "Tyrosine kinase inhibitor combination therapy in first-line treatment of non-small-cell lung cancer : system atic review and network meta-analysis", Onco Targets Ther, 10, pp.2473~2482 (2017)