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

  • 11779

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    P2.11-034 - Indirect comparisons of harm/benefit profile of EGFR tyrosine kinase inhibitors as first line treatment in EGFR mutated NSCLC patients: a systematic review and meta-analysis (ID 2363)

    09:30 - 09:30  |  Author(s): F. Agustoni
    • Abstract

    Background
    To date, three EGFR Tyrosine Kinase inhibitors (TKIs) gefitinib (G), erlotinib (E), and afatinib (A) have been compared to standard chemotherapy as first line treatment in patients with advanced NSCLC harboring EGFR mutations. We performed a systematic review and meta -analysis in order to estimate through indirect comparisons the relative risk benefit associated to each drug.

    Methods
    The major databases were searched for published and unpublished randomized control trial up to March 2013. Data extraction was performed by two independent reviewers and focused on benefit (ORR, PFS) and selected harm outcomes (diarrhea, rash, nail disorders, hypertransaminasemia). The adjusted indirect comparisons were performed using the random effect method described by Bucher and Glenny approach for Hazard Ratio (HR) for PFS and relative risk (RR) for the other outcome measures.

    Results
    All EGFR TKIs fared better when compared with chemotherapy in terms of PFS: overall HR 0.40 (95%CI 0.30-0.54); G vs E HR 1.34 (95%CI 0.63-2.86), G vs A HR 0.74 (95%CI 0.53-1.04), E vs A HR 0.55 (95%CI 0.31-0.99). The relative probability of ORR was G vs E 0.96 (95%CI 0.69-1.34), G vs A 0.79 (95%CI 0.49-1.28), E vs A 0.82 (95%CI 0.49-1.38). Indirect comparisons for safety showed RR for diarrhea G vs E 0.8 (95%CI 0.63-1.01), G vs A 0.32 (95%CI 0.20-0.51), E vs A 0.38 (95%CI 0.24-0.62); for rash G vs E 1.0 (95%CI 0.82-1.22), G vs A 0.31 (95%CI 0.15-0.65), E vs A 0.31 (95%CI 0.15-0.65); for hypertransaminasemia G vs E 2.29 (95%CI 1.63-3.23). Nail disorders affected 57% of patients treated with A, 15% with G, and 4% with E.

    Conclusion
    Results of our analysis showed that all treatments have similar activity and efficacy while the toxicity profile was less favorable for A with a significant higher risk of diarrhea, rash, and nail disorders. Based on these safety results, we suggest that A may not be the first choice for upfront treatment in EGFR mutated patients. Confirmation is warranted by ongoing prospective head to head RCTs.