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M. Giaj Levra



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    P1.06 - Poster Session with Presenters Present (ID 458)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.06-005 - An International Cohort of Patients with Small Cell Lung Cancer after a Non-Small Cell Lung Carcinoma Oncogene or Non-Oncogene Addicted (ID 4531)

      14:30 - 15:45  |  Author(s): M. Giaj Levra

      • Abstract
      • Slides

      Background:
      Phenotypic transformation from Non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a resistance mechanism in tyrosine kinase inhibitors (TKIs) treated EGFR mutant tumors. SCLC is also however less frequently diagnosed in patients without EGFR mutations treated with chemotherapy. These transformations are rare and little is known about the clinical and therapeutic characteristics of these patients. In this study we describe and compare the characteristics of SCLC arising from mutant or non mutant NSCLC.

      Methods:
      We performed a multicentric retrospective collection (27 centers in France and Italy) of cases. Between 2005 and 2015, patients with stage III or IV NSCLC with a secondary transformation to SCLC with histological proof were included.

      Results:
      Forty seven cases of SCLC transformation were collected, 34 in EGFR mutant and 13 in non. Most of the patients (n=37, 82%) were stage IV, (n=27, 57%) female and (n=26, 76%) had an exon 19 mutation. The last treatment before transformation was a TKI in 23 (68%) cases in the mutant group and in 3 (23%) patients (erlotinib) in the non-mutant. Median time to SCLC transformation was 17 [IQR, 11-29] months in the mutant group and 26 [IQR 23-36] months in the other (p=0.03). Molecular analyses were not performed in the non mutant group, 25 (74%) had molecular analyses in the EGFR mutant. A driver mutation was identified in 22/25 (88%) patients: in most of the cases the same as the initial, 1 case of ALK fusion and 1 of PI3K mutation. Thirty patients (88%) received at least one line of treatment after transformation in the mutant group, in all cases a platinum-etoposide (P-E) chemotherapy. Median survival from initial diagnosis in the EGFR mutant group was significantly worse 28 [17-41] months vs 49 [36-118] months in the non EGFR mutant group (p=0.01). After transformation, the same tendency was observed with a median survival of 8 [3-12] months for the EGFR mutated patients vs 13 [6-15] months for the non EGFR mutated patients (p=0.06).

      Conclusion:
      SCLC that occurs in EGFR mutant treated by TKIs is more aggressive than classic SCLC, and differs on epidemiological characteristics. These transformed SCLC are not fully explained and we need to define the molecular characteristics of this cohort, before and after transformation and if funded the whole genome sequencing of the tumors to understand this TKIs mechanism of resistant.

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    P1.07 - Poster Session with Presenters Present (ID 459)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      P1.07-012 - Efficacy of Immune Checkpoint Inhibitors in Large Cell Neuroendocrine Lung Cancer: Results from a French Retrospective Cohort (ID 4613)

      14:30 - 15:45  |  Author(s): M. Giaj Levra

      • Abstract
      • Slides

      Background:
      Nivolumab and pembrolizumab, two programmed death (PD)-1 immune-checkpoint–inhibitor antibodies, demonstrated superiority versus standard chemotherapy in second- third line in both squamous and non-squamous lung cancer. Large cell neuroendocrine lung cancer (LCNEC) is a rare tumour often treated as a small cell lung cancer, but there is not a standard of care after a first line progression. Aim of the study was to assess clinical efficacy of PD-1 inhibitors in these patients.

      Methods:
      We retrospectively reviewed all consecutive LCNEC stage IIIB- IV patients treated with nivolumab or pembrolizumab after platinum-based first line therapy between July 2014 and November 2015 in six French centres. Patients were followed until June 2016. The drugs were given in an early access program or a clinical trial.

      Results:
      The analysis included 10 patients with advanced stage disease. Eight patients (80%) had a stage IV disease with a median age of 59 [interquartile range (IQR) 55-62] years. The majority were males (n=9; 90%), with good performance status (0-1; 9/90%) and 50% were treated in third line or further. Three patients presented brain metastases. In 5 cases a molecular test was done, finding in one case (20%) a KRAS mutation. Patients received a first line treatment with platinum and etoposide in 8 cases (80%) with a disease control rate of 50%. Nine patients received nivolumab and the PD-L1 status was never performed, while the patient treated with pembrolizumab expressed PD-L1. Patients received a median number of 16 [IQR, 13-18] cycles, 6 showed a partial response (60%), 1 a stable disease (10%). Median PFS was 57 [24-57] weeks. Most of the patients stopped treatment due to disease progression (n=4; 80%), only one for a pulmonary interstitial pneumonia.

      Conclusion:
      Our findings suggest that the use of immune-checkpoint–inhibitors in LCNEC could be explored in a larger cohort of patients. This treatment could be considered in the scenario of a disease with limited therapeutic strategy.

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