Author of

• 12648

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  P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

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

  • 12697

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    P3.11-049 - Afatinib in advanced pretreated NSCLC - a Canadian experience (ID 3460)

    09:30 - 09:30  |  Author(s): R. Tudor
    • Abstract

    Background
    Afatinib is an oral, irreversible pan-EGFR inhibitor with demonstrated superiority over first-line chemotherapy in advanced EGFR mutation positive NSCLC. It is also active after failure of chemotherapy and reversible EGFR tyrosine kinase inhibitor (TKI) therapy, with higher response rate and better progression-free survival than placebo (LUX-Lung 1, Miller et al. Lancet Oncol. 2012). Through a national special access program (SAP), Canadian patients with advanced NSCLC, similar to those in the LUX-Lung 1 trial, may access afatinib after exhausting all other available therapies. We report our Canadian experience with afatinib at the two largest centres participating in the SAP.

    Methods
    Retrospective chart review of SAP participants was undertaken at 2 major Canadian cancer centres, the British Columbia Cancer Agency (Vancouver) and Princess Margaret Cancer Centre (Toronto). Demographic, disease and treatment data were abstracted, including toxicity, response (clinically documented tumour reduction), treatment duration and overall survival.

    Results
    From July 2010 to the present, 54 patients at the two sites were treated with afatinib through the SAP. Median age was 59.5 (range 37 to 88 years), 57% were female, 52% were never smokers (7% current, 35% former smokers), 67% had adenocarcinoma histology and 28% were East Asian. 26% had known EGFR mutations (7% wild type, 67% unknown), most commonly exon 19 deletions. Patients received a median of 3 previous therapies (range 2 to 5). All had received prior EGFR TKI therapy (81% erlotinib, 11% gefitinib, 6% both, 2% dacomitinib). Half (47%) had a response to prior EGFR TKI therapy, and 37% experienced grade ≥2 rash and 9% grade ≥2 diarrhea on prior EGFR TKI. The median time from metastatic diagnosis to starting afatinib was 23.1 months. The median treatment duration was 2 months (range 0 – 26). 21% of patients had a response (tumour reduction) to afatinib, 20% stable disease and 50% disease progression as their best response. Median survival from the time of afatinib start was 5 months (95% CI: 2-12 months). The average starting dose of afatinib was 40 mg (6% 50 mg, 94% 40 mg), with 11% requiring dose reduction. One third of patients (34%) stopped treatment for disease progression, 17% for toxicity, 30% for clinical deterioration and 19% for other or unknown reasons. The rate of grade ≥2 diarrhea, rash, paronychia, or stomatitis with afatinib was 17%, 20%, 9%, and 9% respectively (grade ≥3 in 10%, 11%, 5% and 5%). Response (non-RECIST) to afatinib was seen in EGFR wild type (2/4) and mutation positive (3/13) patients. Response to erlotinib or gefitinib was non-significantly associated with response to afatinib (OR 3.3, p=0.22). A similar non-significant association was seen with rash (OR 1.7, p=0.22), but not with diarrhea, (OR 0.37, p=0.45).

    Conclusion
    Afatinib demonstrates activity in clinical practice similar to that reported in LUX-Lung 1. While some required dose reduction, toxicity from afatinib appeared manageable for the majority. Although not significant, there was a propensity to experience response or rash on afatinib if seen with prior EGFR TKI, although this was not seen with diarrhea.