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U. Peretti



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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-032 - Sensitivity and meta-regression analysis exploring potential outcomes predictors in randomized trials (RCTs) evaluating the benefit of 1st-line tyrosine kinase inhibitors (TKIs) for epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma. (ID 1670)

      09:30 - 09:30  |  Author(s): U. Peretti

      • Abstract

      Background
      Patients affected by lung adenocarcinoma carrying a EGFR sensitizing mutation of significantly benefit from TKIs in terms of progression free survival (PFS), activity and symptoms control. The potential predictive role of clinico-pathological predictors should be investigated in order to optimize the benefit of the currently available drugs.

      Methods
      A literature-based meta-regression and sensitivity analyses to investigate the differential effect of TKIs according to demographic and molecular factors, was accomplished, analyzing all RCTs exploring TKIs versus chemotherapy for 1[st]-line treatment of patients affected by EGFR mutant NSCLC.

      Results
      9 trials (3,741 patients) were identified (EGFR mutant: 1,797). 9 RCTs were evaluable for PFS (1,790 patients) and response (1,733 patients); 7/9 for survival (1,075 patients). With regard to PFS and response, a significant interaction according to ethnicity (Asian versus Caucasian versus mixed, p=0.006 [Cochrane-Q 10.275] and p=0.047 [6.129], respectively), and trial design (retrospective versus prospective EGFR analysis, p=0.024 [5.067] and p<0.0001 [13.633]), was found. No difference was observed in term of survival. A significant interaction for response was found, with an Odds Ratio in favour of afatinib, erlotinib and gefitinib (versus chemotherapy) of 2.70 (95% CI 2.11-3.45), 2.67 (95% CI 1.81-3.93) and 1.81 (95% CI 1.46-4.78).

      Interaction [Cochrane-Q] P value Interaction [Cochrane-Q] P value
      PFS Response
      Overall (ERL vs GEF vs AFA) [4.266] p=0.188 [9.924] p=0.007
      ERL vs AFA [3.321] p=0.068 [0.056] p=0.813
      ERL vs GEF [9.714] p=0.054 [5.169] p=0.023
      AFA vs GEF [0.002] p=0.962 [7.351] p=0.007

      Conclusion
      Although limited by the retrospective nature and the heterogeneity, these data indicate a differential effect of TKIs according to the design and the ethnicity, and in response according to TKIs. These data may constitute the background to develop a clinical predictive model to better estimate the expected benefit when using EGFR TKIs in patients with EGFR mutant NSCLC