Maintenance erlotinib versus erlotinib at disease progression inpatients with advanced non-small-cell lung cancer who have notprogressed following platinum-based chemotherapy (IUNO study)

Abstract

Objective: The phase III IUNO trial assessed the benefit of maintenance erlotinib versus erlotinib atprogression in advanced/metastatic non-small-cell lung cancer (NSCLC) that had not progressed fol-lowing four cycles of platinum-based chemotherapy.Materials and Methods: Patients had stage IIIB/IV NSCLC, no known epidermal growth factor recep-tor (EGFR)-activating mutation, and objective response or disease stabilization after platinum-basedinduction chemotherapy. Central EGFR-mutation testing was undertaken on tumors from patients withunknown or wild-type EGFR status following local testing. Patients were randomized to receive blindedmaintenance erlotinib 150 mg/day (‘early erlotinib’) or placebo. Those who progressed on placeboreceived open-label erlotinib (‘late erlotinib’); patients who progressed on erlotinib received approvedsecond-line chemotherapy or best supportive care. Primary endpoint: overall survival (OS).Results: 643 patients were randomized to receive maintenance erlotinib (n = 322) or placebo (n = 321).As of March 23, 2015, 242 (75.2%) OS events had occurred with ‘early erlotinib’ versus 235 (73.2%) with‘late erlotinib’. Median OS was 9.7 and 9.5 months with ‘early erlotinib’ and ‘late erlotinib’, respectively(HR, 1.02, 95% CI: 0.85–1.22; log-rank p = 0.82). No progression-free survival, objective response rate, ordisease control rate benefit was observed with maintenance erlotinib. 410 patients entered the second-line phase of the study: 160 patients (50%) from the maintenance erlotinib arm and 250 patients (78%)from the maintenance placebo arm. The pattern of adverse events (AEs) was consistent with previoustrials; 11 patients who received blinded erlotinib and 3 who received placebo died during the blindedmaintenance phase due to nontreatment-related AEs.Conclusions: OS with maintenance erlotinib was not superior to second-line treatment in patientswhose tumor did not harbor an EGFR-activating mutation. Safety results were consistent with theestablished safety profile of erlotinib. Thus, maintenance treatment with erlotinib in patients withadvanced/metastatic NSCLC without EGFR-activating mutations is considered unfavorable