• Keunchil Park, Chong-Jen Yu, Sang-We Kim, Meng-Chih Lin, Virote Sriuranpong, Chun-Ming Tsai, Jong-Seok Lee, Jin-Hyoung Kang, K C Allen Chan, Pablo Perez-Moreno, Peter Button, Myung-Ju Ahn, and Tony Mok.
• Division of Haematology-Oncology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea.
• JAMA Oncol. 2016 Mar 1; 2 (3): 305-12.

ImportanceContinuing 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.ObjectiveTo study the efficacy of first-line erlotinib therapy in patients with NSCLC with activating EGFR mutations and postprogression erlotinib therapy.Design, Setting, And ParticipantsASPIRATION (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.InterventionsPatients received erlotinib 150 mg/d orally until disease progression, after which erlotinib therapy could be continued at patient and/or investigator discretion.Main Outcomes And MeasuresThe primary end point was 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.ResultsOf 359 patients screened, 208 were enrolled. Median follow-up was 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 PFS1 was 10.8 (95% CI, 9.2-11.1) months. Median PFS1 and PFS2 in the 93 continuing patients was 11.0 (95% CI, 9.2-11.1) and 14.1 (95% CI, 12.2-15.9) months, respectively. Median PFS1 and PFS2 was 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 rate was 66.2%; disease control rate was 82.6%. Median overall survival was 31.0 months (95% CI, 27.3 months to not reached). In the safety population (n = 207) serious adverse events were reported in 27.1%, with events of at least grade 3 experienced by 50.2%. Sensitivity and specificity of plasma-based EGFR mutation analysis was 77% and 92%, respectively.Conclusions And RelevanceASPIRATION 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.Trial Registrationclinicaltrials.gov Identifier: NCT01310036.

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