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P. Archila



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    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P2.01-060 - Biweekly Irinotecan/Bevacizumab in Heavily Treated Advanced NSCLC and Survival According to TIMP1 and EGFR Expression (ID 2521)

      09:30 - 17:00  |  Author(s): P. Archila

      • Abstract
      • Slides

      Background:
      Irinotecan and bevacizumab are effective against non-small cell lung cancer (NSCLC) and synergism with non-cross-resistance has been demonstrated in preclinical studies. Tissue inhibitor of metalloproteinases 1 (TIMP1) and EGFR regulates extracellular matrix catabolism and promotion of cell growth and anti-apoptotic activity in NSCLC.

      Methods:
      Forty nine patients with heavily treated metastatic NSCLC were enrolled from March 2011 to November 2014. Thirty-three (67%) had never been exposed to bevacizumab and 16 had received antiangiogenic therapy as part of their first-line (all had achieved a previous response for more than 6 months). Treatment consisted of a 90-min intravenous infusion of 125 mg/m[2] irinotecan on day 1 and 8 plus 7.5 mg/kg bevacizumab on day 1 (treatment was repeated every 3 weeks). In all patients the mutational status of KRAS and EGFR, as well as TIMP1 and EGFR expression was evaluated.

      Results:
      The median age was 60 years (range, 44-78 years), 57% was male and 75% had ECOG 0-1. The median follow-up was 13.2 months and twenty-three patients had received >3 prior lines. The ORR was 32% (95%CI 22% to 39%) and thirteen patients (26%) achieve stable disease. Median progression-free survival (PFS) rate was 4.4 months (95%CI 2.8-8.3) and median overall survival (OS) rate was 18.0 months (95%CI 16.2-30.7). Nine patients harbouring EGFR mutations had a long-lasting, partial response (>5 months after at least 4 prior lines). Major toxicity was myelosuppression (grade 3 neutropenia occurred in 32% of patients and thrombocytopenia in 8.3%). Three patients experienced febrile neutropenia, one patient suffered grade 4 diarrhoea, and non-haematological toxicity was usually mild. Shorter OS was found in patients with a higher expression of TIMP1 mRNA (P=0.0001) but not according to the expression of EGFR (P=0.14).

      Conclusion:
      Irinotecan plus bevacizumab resulted in favourable activity and manageable toxicity profiles as third or fourth line for patients with advanced NSCLC. Our results suggested that such regimen can represent a reasonable chemotherapeutic option, especially for subjects having EGFR mutations and low expression of TIMP1.

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