First-line erlotinib therapy until and beyond response evaluation criteria in solid tumors progression in Asian patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer the ASPIRATION study

Abstract

Importance: Continuing molecularly targeted treatment beyond disease progression in non-small-cell lung cancer (NSCLC) has appeared promising in retrospective analyses, highlighting the challenge to identify whether progression is the optimal time to switch treatment. Objective: To study the efficacy of first-line erlotinib therapy in patients with NSCLC with activating EGFR mutations and postprogression erlotinib therapy. Design, Setting, and Participants: ASPIRATION (Asian Pacific trial of Tarceva as first-line in EGFR mutation) was a phase 2, open-label, single-arm study conducted from 2011 to 2012 in 23 centers in Hong Kong, Korea, Taiwan, and Thailand of adults with stage IV, EGFR mutation-positive NSCLC, with ECOG performance status 0 to 2. Interventions: Patients received erlotinib 150mg/d orally until disease progression, after which erlotinib therapy could be continued at patient and/or investigator discretion. Main Outcomes and Measures: The primary end pointwas progression-free survival (PFS1; time to Response Evaluation Criteria in Solid Tumours 1.1 progression or death). Secondary end points included PFS2 (time to off-erlotinib progression if erlotinib therapy was extended beyond progression at patient and/or investigator discretion), objective response rate, disease control rate, overall survival, and safety. The use of plasma-based assessment of EGFR mutations was also investigated. Results: Of 359 patients screened, 208were enrolled. Median follow-upwas 11.3 (95%CI, 10.9-13.0) months. Of the 207 intent-to-treat patients (62.3%female; median age, 60.8 [range, 28-89] y), 176 had a PFS1 event (171 progression and 5 deaths); of these, 78 discontinued and 93 continued erlotinib therapy following progression. Median PFS1was 10.8 (95%CI, 9.2-11.1) months. Median PFS1 and PFS2 in the 93 continuing patientswas 11.0 (95%CI, 9.2-11.1) and 14.1 (95%CI, 12.2-15.9) months, respectively. Median PFS1 and PFS2was 11.0 (95%CI, 9.3-12.0) and 14.9 (95%CI, 12.2-17.2) months in patients with exon 19 deletions or L585R mutations. Overall response ratewas 66.2%; disease control ratewas 82.6%. Median overall survivalwas 31.0 months (95%CI, 27.3 months to not reached). In the safety population (n = 207) serious adverse eventswere reported in 27.1%, with events of at least grade 3 experienced by 50.2%. Sensitivity and specificity of plasma-based EGFR mutation analysiswas 77%and 92%, respectively. Conclusions and Relevance: ASPIRATION supports the efficacy of first-line erlotinib therapy in patients with EGFR mutation-positive NSCLC and that treatment beyond progression is feasible and may delay salvage therapy in selected patients.