Author of

• 16549

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  P1.02 - Poster Session with Presenters Present (ID 454)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 16599

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    P1.02-050 - Acquired Resistance to EGFR Tyrosine Kinase Inhibitors (TKIs) in EGFR-Mutant Lung Adenocarcinoma among Hispanics (Rbiop-CLICaP) (ID 5955)

    14:30 - 14:30  |  Author(s): P. Archila
    • Abstract

    Background:
    Patients with epidermal growth factor receptor (EGFR)-mutant lung carcinoma eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKI). In 50% of these cases, a secondary EGFR mutation, T790M, underlies the acquired resistance. Other alterations include amplification of MET, PI3K mutations, changes in MAPK1, Her2, AXL and even transformation to small cell lung carcinoma (SCLC). We assessed histological, clinical characteristics and survival outcomes in Hispanic patients with EGFR mutation after disease progression.
    
    Methods:
    34 EGFR-mutant lung cancer patients with acquired resistance to EGFR TKIs were identified as part of a prospective registry (active between January 2011 and January 2015) in which post-progression tumor specimens were collected for molecular analysis using SNaPshot tumor genotyping assay to detect mutations in EGFR, KRAS, BRAF, PI3KCA, TP53, MET and Her2, and FISH for MET, ALK and EGFR. Samples also underwent immunohistochemistry analysis for E-cadherin, synaptophysin, CD56 and PDL1. Post-progression interventions, response and survival were assessed and compared to those with and without T790M.
    
    Results:
    Mean age was 59.4±13.9 years; 62% were female, 65% were never-smokers and 53% had a performance status ≥80%; main metastatic sites were lung (16/47%), bone (20/58%), brain (18/52%) and liver (13/38%). All patients received erlotinib as first- line treatment and documented mutations were: 60% DelE19 (Del746–750) and 40% L858R. Overall response rate (ORR) with first line TKI was 61.8% and progression free survival (PFS) was 16.8 months (range, 13.7–19.9 m). After progressing to TKI, all patients were re-biopsied, of whom 16 had the T790M mutation (47.1%); 5 had PI3K mutations (14.7), 5 had EGFR amplification (14.7%), 2 had a KRAS mutation (5.9%), 3 had MET amplification (8.8%), 2 had Her2 alterations (5.8%, deletions/insertions in e20), and one had SCLC transformation (2.9%). 79.4% received treatment after progression. ORR for post-TKI treatments was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (CI95% 2.2–36.6). There were no differences in PFS according to gender (p=0.10) or type of acquired alteration (p=0.63). Median survival was 32.9 months (CI95% 30.4–35.3), and only the use of post-progression therapy affected OS in multivariate analysis (p=0.05).
    
    Conclusion:
    Hispanic patients with acquired resistance to EGFR TKIs continued to be sensitive to other treatments after progression. Proportion of T790M+ patients appears to be similar to previously reported results in Caucasians.
    
    

• 18606

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  P3.03 - Poster Session with Presenters Present (ID 473)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18651

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    P3.03-045 - Treatment of Malignant Pleural Mesothelioma beyond First-Line among Hispanics (MeSO-CLICaP) (ID 6271)

    14:30 - 14:30  |  Author(s): P. Archila
    • Abstract

    Background:
    Platinum/Pemetrexed chemotherapy is standard of care in first-line (FL) treatment of malignant pleural mesothelioma (MPM). Different second and third lines regimens are also considered, but the optimal treatment has not yet been defined.
    
    Methods:
    The aim of this study was to evaluate clinical outcomes of second (SL) and third line (TL) therapies in a series of MPMs included in a retrospective multinational database (MeSO-CLICaP). Clinical records of MPM-patients who received treatment beyond FL from 2008 to 2016 were reviewed. Study endpoints were response, overall-survival (OS), and progression-free-survival (PFS) for SL and TL, stratified for patient characteristics, FL-outcomes, and type of regimen. Out of 124 patients, 79 received SL/TL and had sufficient clinical data.
    
    Results:
    Of the 124 patients included in the MeSO-CLICaP registry, 79 (64%) received some treatment after first line. Median age was 59 years (range 33-81), 42 (53%) were men, 74% were current or former smokers and 77% had a baseline ECOG 0-1. After FL, 57 patients (76%) achieved disease-control (PR 24/32% and SD 33/44%) and 18 had a time-to-progression ≥8 months. Median PFS and OS to SL were 6.2 (95%CI 4.9-7.4) and 16.1 (95%CI 14.5-17.6) months, respectively. According to a multivariate analysis, disease control after SL-therapy was significantly related to pemetrexed-based treatment (OR 2.46; p=0.017) and FL-TTP≥12 months (OR 3.50; p=0.006). Improved PFS to SL was related to younger age (<65 years, HR: 0.60; p=0.045), ECOG 0-1 (HR 0.72; p=0.02), and FL-TTP≥12 months (HR 0.48; p<0.001). OS was significantly related to ECOG 0-1 (HR 0.43; p=0.011) and to FL-TTP≥12 months (HR 0.66; p=0.05). Fifty-two patients (42%) receive a TL achieving a disease control rate of 62% with a PFS of 5.9 months (95%CI 5.0-6.8).
    
    Conclusion:
    SL-chemotherapy appears to be active in Hispanic MPM-patients, particularly in younger patients with good PS and prolonged disease control with FL chemotherapy. Considering the important limitations of this study, due to retrospective nature and the possible selection bias, prospective clinical trials are warranted to clarify these issues.