Rationale and Design of a Phase II Trial of Osimertinib Combined With Bevacizumab in Patients With Untreated Epidermal Growth Factor Receptor-mutated Non-small-cell Lung Cancer and Malignant Pleural and/or Pericardial Effusion (SPIRAL II Study).

Progression-free survival (PFS) of patients with non-small-cell lung cancer with pleural or pericardial effusion is expected to be prolonged with combination use of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor plus bevacizumab compared with that with an EGFR-tyrosine kinase inhibitor alone. Phase I clinical trial data have been reported for combined treatment with osimertinib plus bevacizumab and demonstrated their safety, but the efficacy remains unclear, particularly in patients with pleural or pericardial effusion. This is an ongoing single arm, prospective, open-label, multicenter, phase II trial to evaluate the efficacy and safety of osimertinib plus bevacizumab combination therapy in EGFR mutation-positive patients with untreated or recurrent non-small-cell lung cancer and pleural and/or pericardial effusion. Osimertinib will be administered orally once daily at a dose of 80 mg. One cycle consists of 21 days. Bevacizumab 15 mg/kg will be administered by drip infusion on Day 1 of each cycle. Treatment will be continued until progressive disease or any of the discontinuation criteria are met. The primary endpoint will be the 1-year PFS rate. Secondary endpoints are response rate, PFS, overall survival, survival not requiring pleural/pericardial drainage, and safety. Osimertinib plus bevacizumab combination therapy is expected to prolong PFS and reduce adverse events. TRIAL REGISTRATION NUMBER: UMIN000028071.