A multicenter, phase 2 trial is planned to evaluate the efficacy and safety of osimertinib among patients with EGFR mutation-positive non-small cell lung cancer (NSCLC) who experienced either isolated central nervous system (CNS) progression or systemic progression after treatment with a first- or second-generation EGFR tyrosine kinase inhibitor (TKI), according to a report published in Clinical Lung Cancer.
Osimertinib is a standard of care for the treatment of advanced NSCLC with EGFR activating mutations in the first line; however, currently only patients with metastatic disease harboring the T790M mutation are eligible for osimertinib as second-line therapy. Given that approximately 50% of patients are therefore ineligible for osimertinib after a first- or second-generation EGFR TKI, the trial aims to evaluate the role of osimertinib in this population.
The multicenter, phase 2 WJOG12819L trial will enroll 17 patients with isolated CNS progression of NSCLC into cohort 1 and 53 patients with systemic disease progression in cohort 2. All patients will have EGFR mutation-positive NSCLC with negative or unknown T790M status.
Patients in both cohorts will have previously received a first- or second-generation EGFR TKI. In cohort 2, patients will have also received platinum-doublet chemotherapy after systemic progression.
Both cohorts will receive osimertinib 80 mg/d until disease progression.
The primary endpoints differ for each cohort. For cohort 1, response rate of metastatic brain lesions will be the primary endpoint, and safety will be the secondary endpoint. For cohort 2, response rate will be the primary endpoint, and progression-free survival, disease control rate, overall survival, and safety will be the secondary endpoints.
The authors concluded that “our phase 2 trial plans to prospectively evaluate the efficacy of osimertinib for these patients and thereby evaluate the efficacy of osimertinib for these patients and thereby potentially gain approval for expansion of the indications for osimertinib in Japan.”
Takeda M, Shimokawa M, Nakamura A, et al. A phase II study to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC who developed isolated CNS progression (T790M-negative or unknown) during first- or second-generation EGFR-TKI or systemic disease progression (T790M-negative) after treatment with first- or second-generation EGFR-TKI and platinum-based chemotherapy (WJOG12819L). Clin Lung Cancer. Published online January 25, 2021. doi:10.1016/j.cllc.2020.12.009