Author of

• 11745

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  P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11760

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    P2.11-015 - Comparative effectiveness of gefitinib, erlotinib, afatinib and chemotherapy in the first line treatment of patients with advanced non small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations (ID 1533)

    09:30 - 09:30  |  Author(s): B. Haaland
    • Abstract

    Background
    EGFR tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with advanced NSCLC who harbor activating EGFR mutations. No large prospective trial has compared gefitinib, erlotinib and afatinib face-to-face. We did a network analysis comparing the three drugs against chemotherapy and among themselves.

    Methods
    We searched PUBMED, EMBASE, google scholar databases and abstracts from ASCO, ESMO and WCLC abstracts between 2000 and 2013 using relevant search terms. Prospective, randomized clinical trials comparing erlotinib, gefitinib, or afatinib to chemotherapy or one another as first-line therapy in patients with non-small-cell lung cancer were selected. Studies were included if they included only patients with EGFR activating mutations or if they reported relative efficacy within the EGFR positive subgroup. Endpoints of interest were progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). Direct and indirect meta-estimates were generated in the context of linear mixed effects models, similar to the model of DerSimonian and Laird, with fixed effects for each relative comparison and random effects for each study. Heterogeneity across studies was tested using chi-squared and I[2] statistics in the manner of Higgins and Thompson. Confidence (CI) and Predictive intervals (PIs) were calculated using the study-to-study variance estimates from each linear mixed-effects model. Results were considered statistically significant if the CI and PI did not cross unity.

    Results
    Eight studies fulfilled search and inclusion criteria: OPTIMAL, EURTAC, LUX-Lung 3, LUX-Lung 6, IPASS, West Japan, North-east Japan, and First-SIGNAL. The pooled hazard ratio (HR) meta-estimate for PFS were as follows: erlotinib vs. chemotherapy - 0.25 (95% CI 0.14-0.43; 95% PI 0.11-0.58), afatinib vs. chemotherapy - 0.44 (95% CI 0.25-0.77; 0.19-1.03), gefitinib vs. chemotherapy - 0.43 (95% CI 0.29-0.63; 95% PI 0.21-0.90), erlotinib vs. afatinib - 0.57 (95% CI 0.26-1.23; 95% PI 0.21-1.55), erlotinib vs. gefitinib - 0.58 (95% CI 0.30-1.13; 95% PI 0.23-1.46), and afatinib vs. gefitinib - 1.02 (95% CI 0.52-2.00; 95% PI 0.41-2.58). The test of heterogeneity (for PFS) indicated moderately high study-to-study variability with Q = 17.7 on 5 degrees of freedom (p = 0.003) and I[2] of 72%. For ORR, The pooled odds ratio (OR) meta-estimate for erlotinib vs. chemotherapy was 8.2 (95% CI 4.5-15.1; 95% PI 3.9-17.5), afatinib vs. chemotherapy was 5.5 (95% CI 3.4-8.8; 95% PI 2.9-10.5), gefitinib vs. chemotherapy was 4.1 (95% CI 2.7-6.3; 95% PI 2.3-7.6), erlotinib vs. afatinib was 1.5 (95% CI 0.7-3.3; 95% PI 0.6-3.7), erlotinib vs. gefitinib was 2.0 (95% CI 0.9-4.1; 95% PI 0.8-4.7), and afatinib vs. gefitinib was 1.3 (95% CI 0.7-2.5; 95% PI 0.6-2.8). The test of heterogeneity indicated moderate study-to-study variability with Q = 7.32 on 5 degrees of freedom (p = 0.198) and I[2] of 32% (For ORR). There were no statistically significant differences for overall survival.

    Conclusion
    Erlotinib, gefitinib and afatinib improved clinical outcomes when compared with chemotherapy. There were no statistically significant differences in the comparison among erlotinib, afatinib, and gefitinib.