Author of

• 10801

  +

  P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 2
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10802

    +

    P1.11-001 - Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) related interstitial lung disease in Taiwanese patients with non-small cell lung cancer (ID 261)

    09:30 - 09:30  |  Author(s): C. Chiu
    • Abstract

    Background
    In the recent years, it has been shown that epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), gefitinib or erlotinib, can provide significant benefit to patients with advanced non-small cell lung cancer (NSCLC). A major concern during EGFR-TKI treatment is the development of interstitial lung disease (ILD). The incidence and clinical characteristics of ILD associated with EGFR-TKIs in Taiwanese patients are less well defined.

    Methods
    Patients with advanced NSCLC in the Taipei Veterans General Hospital were screened and patients who had received EGFR-TKIs were enrolled in this study. The clinical information including medical records and chest images were reviewed. The diagnosis of EGFR-TKI related ILD was confirmed by two pulmonologists according to previously published criteria. Association between ILD development and clinical factors was evaluated.

    Results
    From February 2008 to July 2012, a total of 1214 patients who received EGFR-TKI as single therapy for NSCLC were screened. Patients who developed severe ILD and needed hospitalization (grade 3-5) were included. Consequently, 9 of 1214 patients (0.7%) were diagnosed to have severe EGFR-TKI related ILD. The median age of the patients with ILD was 61.0 years and 6 were male (66.7%). The median time interval from EGFR-TKIs use to onest of ILD was 31 days (range: 10-75 days). The most common symptom of EGFR-TKIs related ILD was dyspnea (88.9%). The most common radiological manifestation was bilateral ground glass opacity (GGO), which was noted in 5 patients (55.6%). All patients discontinued EGFR-TKIs immediately when ILD was suspected and 8 patients (88.9%) received systemic steroids. Six of nine patients (67%) patients died from ILD.

    Conclusion
    EGFR-TKIs, both gefitinib and erlotinib may cause fatal ILD in Taiwanese NSCLC patients. Physicians should be aware of this rare but severe side effect of EGFR-TKI and monitor this pulmonary toxicity closely.

  • 10835

    +

    P1.11-035 - Outcomes of Afatinib-Based Regimens for Salvage Treatment of Advanced Stage Non-Small Cell Lung Cancer (NSCLC) Patients Who Had Been Heavily Pretreated (ID 2505)

    09:30 - 09:30  |  Author(s): C. Chiu
    • Abstract

    Background
    The therapeutic development for advanced stage NSCLC has improved in the past decade, but the poor treatment outcome still poses a major challenge. Investigators have combined conventional platinum-based chemotherapy with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), in the hope of achieving greater therapeutic efficacy. However, current data show that the combination strategy has repeatedly failed to provide a better survival benefit, irrespective of the mutation status of the tumors. However, it might not be true for combination of EGFR-TKI with individual agents which exhibit a variety of anti-cancer actions. Afatinib, a novel irreversible ErbB-family blocker, has shown to provide efficacious effects for advanced stage NSCLC patients. From the Phase I data, afatinib in combination with chemotherapy or anti-EGFR therapy exhibited tumor inhibition response. We present retrospective clinical evidences of patients from Compassionate Usage Program. These patients are treated with continuation of afatinib in combination, alternately, with various chemotherapies or anti-EGFR therapy.

    Methods
    Between August 2012 to February 2013, 37 patients were enrolled for the program, 11 of these patients died of disease progression either received afatinib for less than 2 weeks or never started afatinib treatment, the remaining 26 patients were included in this analysis. Patient characteristics are median age was 67 (range 46-84), gender (male/female = 8/18), ECOG status (PS 1/2/3: 16/2/4), EGFR mutation status (exon 19 deletion = 10; L858R mutation = 6; exon 18 mutation = 1; wild type = 5; unknown = 5). All of these patients had been previously treated with either gefitinib or erlotinib with no disease progression for more than 6 months. The median TKI-free interval was 125 days (range 0-1,450 days); 8 patients had no TKI-free interval. All patients but 1 started the treatment of afatinib monotherapy (30 mg or 40 mg daily), and subsequently, either paclitaxel (60 mg/m2, day 1, 8, and 15, 4-week cycle), docetaxel (30 mg, day 1, and 8, 3-week cycle), or cetuximab (250mg/m2, every 2 weeks) was added. The combination was alternated or discontinued when patient had disease progression according to RECIST criteria version 1.1, intolerability or severe toxicity.

    Results
    Of the whole group of patients, 25 received afatinib monotherapy, 11 with 1 afatinib doublet (afatinib/cetuximab = 3; afatinib/paclitaxel = 6; afatinib/docetaxel = 2); 2 with 2 afatinib doublets (afatinib/cetuximab and afatinib/docetaxel = 1; afatinib/cetuximab and afatinib/docetaxel = 1) and 1 with 3 afatinib doublets (afatinib/cetuximab, afatinib/paclitaxel and afatinib/docetaxel). The median duration from administration of frontline systemic treatment to initiation of afatinib was 3 years (range 1 - 10 years). These patients had received 2 to 7 (median 5) lines of treatment before receiving afatinib-based treatment. The median time to treatment failure was 223 days (95% CI: 217, 249) and median overall survival was 288 days (6 events). The toxicities were mild and manageable. There was no correlation between the values of TKI-free interval and duration of afatinib monotherapy.

    Conclusion
    Integration of afatinib with various treatment agents based on different treatment rationales, the afatinib-based treatment may potentially extend treatment duration and patient survival.