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D.D. Liu



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    O02 - NSCLC - Combined Modality Therapy I (ID 111)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Combined Modality
    • Presentations: 1
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      O02.03 - Value of Adding Erlotinib to Thoracic Radiation Therapy with Chemotherapy for Stage III Non-Small Cell Lung Cancer: A Prospective Phase II Study (ID 2436)

      10:30 - 12:00  |  Author(s): D.D. Liu

      • Abstract
      • Presentation
      • Slides

      Background
      The molecular basis for radiation resistance seems to involve an enhanced survival response with increased capacity for DNA repair and suppressed apoptosis. Both properties are controlled in part by upstream signal transduction pathways triggered by activation of the epidermal growth factor receptor (EGFR). Hypothesizing that the response of non-small cell lung cancer (NSCLC) to current standard chemoradiotherapy can be improved through the addition of therapy targeted to the epidermal growth factor receptor (EGFR), we undertook a single-institution phase II trial to test whether adding the EGFR tyrosine kinase inhibitor (TKI) erlotinib to concurrent chemoradiation therapy for previously untreated, locally advanced, inoperable NSCLC would improve survival and response rates without increasing toxicity.

      Methods
      Forty-eight patients with previously untreated NSCLC received radiation (63 Gy/35 fractions) on Monday‒Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin AUC=2) given every Monday and erlotinib (150 mg orally 1/d) Tuesday–Sunday for 7 weeks, followed by two cycles of consolidation paclitaxel-carboplatin. The primary endpoint was time to progression; secondary endpoints were toxicity; response, overall survival (OS), and disease control rates; and whether any endpoint differed by EGFR mutation status.

      Results
      Of 46 patients (96%) evaluable for response, 40 were former or never smokers; 23 had adenocarcinoma; and 41 were evaluable for EGFR mutations (37 wild-type [wt] and 4 mutations [all adenocarcinomas]). Median time to progression was 14.5 months and did not differ according to EGFR status. Toxicity was acceptable (no grade 5, one grade 4, and eleven grade 3). Fourteen patients (31%) had complete responses (3 mutations and 11 wt), 24 (52%) partial (20 wt and 4 unknown EGFR mutation status), and 8 (18%) had stable or progressive disease (6 wt, 1 mutation and 1 unknown EGFR mutation status); 3 patients with mutations (75%) had complete response vs. 11 wt (30%) (p=0.07 for EGFR mutation vs wt groups). For alive patients, the median follow-up was 44.7 months’ follow-up (range, 29.3–54.6 months). OS rates were 82.6% at 1 year, 67.4% at 2 years, 48.5% at 3 years, and 32.2% at 4 years and did not differ by mutation status (wt vs mutation, p=0.17). For all patients the median follow-up was 30.6 months’ follow-up (range, 3.4–54.6 months). 14 patients were free from progression and 32 had local failure, distant failure, or both. Eleven of the 27 distant failures were in the brain (7 wt, 3 mutation, 1 unknown; P=0.04); the local control rate was 75% among the 4 patients with EGFR mutations. Median time to progression was 13.6 months (95% confidence interval 10.2-20) and did not differ by EGFR status (wt vs mutation p=0.39).

      Conclusion
      Overall survival was promising, but time to progression was disappointing. Toxicity was acceptable. The prevalence of distant failures underscores the need for more effective systemic therapy, perhaps including maintenance EGFR-TKI for patients with mutated EGFR.

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