Study Protocol
Rationale and design of a phase II trial of osimertinib as first-line treatment for elderly patients with epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer (SPIRAL-0 study)
Abstract
Background: Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has a potent inhibitory effect against both T790M resistance mutations and EGFR-TKI sensitizing in EGFR, with a relatively low affinity for wild-type EGFR. Osimertinib has been approved as a therapeutic agent for patients with T790M-mutation positive advanced non-small cell lung cancer. As a first- line treatment, osimertinib may significantly prolong progression-free survival (PFS) in comparison with the earlier generation first-line standard treatment. Osimertinib has been reported to provide survival benefits to EGFR mutation-positive patients. However, the efficacy and safety of osimertinib as a first-line treatment for patients aged ≥75 years remains to be established.
Methods: In this single arm, prospective, open-label, multicenter, phase II trial, 40 subjects aged ≥75 years with EGFR mutation-positive advanced non-small-cell-lung cancer will be recruited. Patients will be treated with osimertinib 80 mg/day until disease progresses or until the patient meets a discontinuation criterion. The primary endpoint is one-year PFS. Secondary endpoints are overall response rate, PFS, overall survival, and safety. Thirty-seven patients are required for the present study, as calculated based on normal approximation with a one-sided α level of 5% and 80% power, assuming that the expected one-year PFS is 70% and the 1-year PFS threshold is 50%.
Discussion: We are conducting an intervention study to investigate the safety and efficacy of osimertinib as a first-line treatment agent for EGFR mutation-positive NSCLC in patients aged ≥75 years.
Trial registration number: jRCTs071180007
Methods: In this single arm, prospective, open-label, multicenter, phase II trial, 40 subjects aged ≥75 years with EGFR mutation-positive advanced non-small-cell-lung cancer will be recruited. Patients will be treated with osimertinib 80 mg/day until disease progresses or until the patient meets a discontinuation criterion. The primary endpoint is one-year PFS. Secondary endpoints are overall response rate, PFS, overall survival, and safety. Thirty-seven patients are required for the present study, as calculated based on normal approximation with a one-sided α level of 5% and 80% power, assuming that the expected one-year PFS is 70% and the 1-year PFS threshold is 50%.
Discussion: We are conducting an intervention study to investigate the safety and efficacy of osimertinib as a first-line treatment agent for EGFR mutation-positive NSCLC in patients aged ≥75 years.
Trial registration number: jRCTs071180007
