Pooled Analysis of Clinical Outcomes for Patients with EGFR Mutations in Non-Small-Cell Lung Cancer: An Update

ABSTRACT Background In 2010, the results of a pooled analysis examining the correlation of EGFR mutations with clinical outcome were reported [1]; EGFR TKIs appeared to be the most effective treatment for EGFR mutation-positive NSCLC. Since this report, more trials (including large controlled phase III studies) have been published, doubling the number of eligible patients. An updated analysis was carried out to provide a comprehensive dataset assessing the treatment of EGFR mutation-positive NSCLC. Methods Congress reports and papers reporting progression-free survival (PFS) for EGFR mutation-positive NSCLC treated with chemotherapy, erlotinib or gefitinib (phase II/III studies/retrospective analyses) were identified in a literature search and checked for duplication. Most papers report high level results e.g. median PFS. Calculations were based on simplifying assumptions to allow for pooling of results and to obtain an accuracy estimate (surrogate for confidence intervals). The pooled median PFS, MPFS(all), was estimated by a study-size N (i) weighted average: MPFS(all)= 1/N(all)∑N(i)MPFS(i). The potential for publication bias was assessed using funnel plots. Permutation testing will be carried out. For full methodology see [1]. Results Data were included from 20 chemotherapy studies (n = 984; updated from n = 375 [1]), 27 erlotinib studies (n = 735; from n = 365 [1]), and 56 gefitinib studies (n = 1843; from n = 1069 [1]). Longer PFS was seen with both EGFR TKIs compared with chemotherapy across treatment lines (Table). Conclusion In the past three years, several important studies have examined EGFR TKI therapy in patients with EGFR mutation-positive NSCLC. This updated dataset provides a comprehensive picture of treatment outcomes in this patient subset, confirming that this subgroup derives a greater benefit from EGFR TKIs than from conventional chemotherapy, especially when administered as first line. [1] Paz-Ares J Cell Mol Med 2010 Pooled median PFS (95% accuracy interval) for patients with EGFR mutation-positive tumours Single-agent erlotinib All lines of therapy (n = 735) 12.4 months (11.6–13.4) * Predominantly first-line (n = 354) 12.0 months (10.8–13.3) Single-agent gefitinib All lines of therapy (n = 1843) 9.3 months (8.9–9.8) * Predominantly first-line (n = 716) 9.7 months (9.0–10.5) Chemotherapy (may be single- or multiple-agent treatment) All lines of therapy (n = 984) 5.6 months (5.3–6.0) * Predominantly first-line (n = 868) 5.8 months (5.5–6.2) * Predominantly first-line is ≥90% of patients treated in first-line setting Disclosure L. Paz-Ares: Advisory board: Roche. D. Soulieres: Advisory board: Roche, Boehringer Ingelheim. B. Klughammer: Stock ownership: F. Hoffmann-La Roche Ltd Employed by F. Hoffmann-La Roche Ltd. I. Bara: Employed by F. Hoffmann-La Roche Ltd. J. Moecks: Corporate sponsored research in biomathematics for Roche in several fields Former employee of F. Hoffmann-La Roche Ltd. T.S.K. Mok: Advisory board:AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, BeiGene, AVEO, Pfizer, Taiho, BI, GSK Biologicals On the Board of Directos for IASLC Corporate sponsored research for AstraZeneca Employed by The Chinese University of Hong Kong