RECIST progression patterns during EGFR tyrosine kinase inhibitor treatment of advanced non-small cell lung cancer patients harboring an EGFR mutation.

Abstract Background Progression patterns at the response evaluation criteria in solid tumors-progressive disease (RECIST-PD) during treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for advanced non-small cell lung cancer (NSCLC) in patients harboring an EGFR mutation are clinically heterogeneous. We evaluated the association between progression patterns during EGFR-TKI treatment and prognosis after treatment in such patients. Methods From 2008 to 2012, 160 consecutive patients with advanced NSCLC harboring an EGFR mutation were treated with EGFR-TKIs (erlotinib or gefitinib). Among these, 104 who experienced RECIST-PD were retrospectively evaluated for initial response to EGFR-TKIs, progression sites, focus of progression (solitary lesion or multiple lesions), symptom status at RECIST-PD evaluation, and post-progression survival (PPS). Results Of 104 patients, 96 (92%) had an EGFR major mutation, and 50 (48%) received EGFR-TKIs as first-line treatment. Overall response rate and median time to RECIST-PD on EGFR-TKIs were 68% and 8.2 months, respectively. At the time of attaining RECIST-PD status, 44 (42%) patients were symptomatic, and 60 (58%) were asymptomatic. Progression sites at RECIST-PD were isolated brain in 17 (16%) patients and systemic in 87 (84%): 24 (23%) had a solitary lesion, and 80 (77%) had multiple lesions. After RECIST-PD assessment, 40 (38%) patients continued EGFR-TKIs, and 25 (24%) switched to cytotoxic agents; 10 (10%) received local radiotherapy for an isolated progression site (brain 6; bone 3; lung 1). Median PPS was 10.8 months. Multivariate analysis revealed that asymptomatic or solitary lesion status was associated with significantly longer PPS (asymptomatic: HR 0.36, 95% CI 0.21–0.62, P  P  = 0.04). Conclusions Progression patterns at the RECIST-PD during EGFR-TKI treatment of advanced NSCLC in patients harboring an EGFR mutation are widely diverse, and might be associated with clinical outcome after treatment failure.