Efficacy of lazertinib for symptomatic or asymptomatic brain metastases in treatment‐naive patients with advanced EGFR mutation‐positive non‐small cell lung cancer: Protocol of an open‐label, single‐arm phase II trial

• Published in: Thoracic cancer 2023-08, Vol.14 (22), p.2233-2237
• Main Authors: Lee, Bora, Ji, Wonjun, Lee, Jae Cheol, Song, Si Yeol, Shin, Young Seob, Cho, Young Hyun, Park, Ji Eun, Park, Hyungjun, Choi, Chang‐Min
• Format: Article
• Language: English
• Subjects: Asymptomatic; Brain cancer; brain metastases; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Clinical Trials, Phase II as Topic; Decision trees; Effectiveness; epidermal growth factor receptor; ErbB Receptors; Humans; Informed consent; Intracranial pressure; lazertinib; Lung cancer; Lung diseases; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Magnetic resonance imaging; Medical prognosis; Metastasis; Mutation; Nervous system; non‐small cell lung cancer; Protein Kinase Inhibitors - pharmacology; Radiation therapy; Response rates; Study Protocol; Surgery; Tumors
• ISSN: 1759-7706; 1759-7714
• DOI: 10.1111/1759-7714.15018

Introduction Non‐small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation has a higher incidence of brain metastases than wild‐type EGFR mutations. Osimertinib, a third‐generation EGFR tyrosine kinase inhibitor (TKI), targets both EGFR‐TKI sensitizing and T790M‐resistance mutations and has a higher brain penetration rate relative to first‐ and second‐generation EGFR‐TKIs. Therefore, osimertinib has become a preferred first‐line therapy for advanced EGFR mutation‐positive NSCLC. However, lazertinib, an emerging EGFR‐TKI, has shown higher selectivity toward EGFR mutations and improved penetration of the blood–brain barrier compared to osimertinib in preclinical studies. This trial will evaluate the efficacy of lazertinib as a first‐line therapy in patients with EGFR mutation‐positive NSCLC who have brain metastases, with or without additional local therapy. Methods This is a single‐center, open‐label, single‐arm phase II trial. A total of 75 patients with advanced EGFR mutation‐positive NSCLC will be recruited. Eligible patients will receive oral lazertinib 240 mg, once daily until disease progression or intolerable toxicity is detected. Patients with moderate to severe symptoms related to brain metastasis will simultaneously receive local therapy for the brain. The primary endpoints are progression‐free survival and intracranial progression‐free survival. Discussion Lazertinib, in combination with local therapy for the brain, if necessary, is expected to improve the clinical benefit in advanced EGFR mutation‐positive NSCLC with brain metastases, as a first‐line treatment. Based on previous studies, the efficacy of lazertinib for brain metastasis is anticipated to be satisfactory in EGFR mutation‐positive NSCLC. This is the protocol for a single‐center, single‐arm phase II trial that will evaluate the efficacy of lazertinib with or without local therapy as a first‐line treatment of patients with EGFR mutation‐positive NSCLC, who also present with brain metastases.