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  Lunch & Poster Display session (ID 58)

  • Event: ELCC 2019
  • Type: Poster Display session
  • Track:
  • Presentations: 3
  • Moderators:
  • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1

  • 29084

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    150P - Characterization of patients with metastatic non-small cell lung cancer obtaining long term benefit from immunotherapy (ID 321)

    12:30 - 13:00  |  Presenting Author(s): Giulia Galli
    • Abstract
    • Slides

    Background
    

    The indications of Immunotherapy (IO) for metastatic Non Small Cell Lung Cancer (mNSCLC) are broadening. Although different studies have proved the efficacy of IO in this setting, only a minority of patients (pts) gains advantage from IO and predictive variables of Long Term Benefit (LTB) are incompletely understood.

    a9ded1e5ce5d75814730bb4caaf49419 Methods
    

    We retrospectively collected data about all consecutive mNSCLC pts treated with IO at Istituto Nazionale dei Tumori, Milan, Italy, from 04/2013 to 07/2017. We defined pts with LTB as those obtaining a Complete Response (CR), a Partial Response (PR) or a Stable Disease (SD) as best response from IO and maintaining it for ≥12 months (mos). Pts were defined to have a Short Term Benefit (STB) if they obtained a CR, a PR or a SD as best response but maintained it for <12 mos. Pts were defined as Progressors (P) If they obtained a progression as best response. Fisher’s test was used to compare variables. Multivariate analyses were performed with logistic regression. Survival was estimated with Kaplan-Meier method.

    20c51b5f4e9aeb5334c90ff072e6f928 Results
    

    One hundred forty-seven pts were identified. IO was an antiPD1 in 87 cases, an antiPDL1 in 52 cases, a combination antiPDL1/PD1 + antiCTLA4 in 7 cases, an antiCTLA4 in 1 case. First line IO was administered in 19 pts, II line IO in 63 pts, ≥III line IO in 64 pts. After a median follow up of 28.5 mos, 35 pts obtained LTB from IO. A higher proportion of LTB pts compared with controls (STB + P) showed CR/PR as first (12/35 vs 10/112, p = 0.0007) and best response (19/35 vs 14/112, p < 0.0001) to IO. More LTB pts than controls had a neutrophil/lymphocyte ratio<5 (p = 0.0378) and did not receive steroids (p = 0.0023), but only the evidence of a CR/PR during IO retained association to LTB at multivariate analyses (p = 0.0002). All other clinical and pathologic variables appeared unremarkable. A second analysis comparing pts with LTB and STB confirmed this result (odds ratio for CR/PR vs SD: 2.629, 95%CI: 1.051-6.579; p = 0.0427).

    fd69c5cf902969e6fb71d043085ddee6 Conclusions
    

    Objective response appears to be a central factor in predicting LTB from IO, irrespective of all other variables. If confirmed, this observation could help in identifying the pts with mNSCLC candidate to gain the highest advantage from IO.

    b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
    

    The authors.

    213f68309caaa4ccc14d5f99789640ad Funding
    

    Has not received any funding.

    682889d0a1d3b50267a69346a750433d Disclosure
    

    All authors have declared no conflicts of interest.

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  • 29094

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    160P - EPSILoN score: Validation cohort of a prognostic score in advanced non-small cell lung cancer (aNSCLC) patients treated with immunotherapy (ID 494)

    12:30 - 13:00  |  Author(s): Giulia Galli
    • Abstract
    • Slides

    Background
    

    Despite the benefit in overall survival (OS), only 18-20% of aNSCLC patients (pts) respond to immunotherapy (IO) in second-line (2nd) with a median progression-free survival (mPFS) of 2-4 months (mo). We previously reported the role of EPSILoN score (Ecog-Ps, Smoke, lIver, Ldh, Nlr) as a clinical and biochemical prognostic score of survival in 154 pts treated with 2nd IO. In this study we aim to validate the EPSILoN score in a different patient population group treated with IO in the same setting.

    a9ded1e5ce5d75814730bb4caaf49419 Methods
    

    We enrolled 193 eligible patients at the National Cancer Institute of Milan, Italy. From 193 aNSCLC patients receiving single-agent anti-PD-(L)-1 as 2nd (61%) and ≥ 3rd line (39%) we collected baseline complete blood cell count and estimated their ratio such as neutrophil-lymphocyte ratio (NLR). Also we evaluated baseline LDH level. Survival analyses using Kaplan–Meier method and multivariate analysis (Cox progression model) were performed to identify and confirm independent variables.

    20c51b5f4e9aeb5334c90ff072e6f928 Results
    

    Of 193 pts mPFS and mOS were 2.3 and 7.6 mo, respectively. Univariate and multivariate analyses for PFS adjusted for age, sex, smoke status, ECOG-PS, histology, disease site, confirmed heavy smoking status (≥40 pack/years) (HR 0.71, p = 0.036) and baseline LDH <400 mg/dl (HR 0.66, p = 0.026) as independent positive factors while ECOG-PS 2 (HR 1.79, p < 0.001), baseline liver mets (HR 1.48, p = 0.04) and NLR≥4 (HR 1.49, p = 0.029) as negative factors. The five baseline clinical and blood biomarkers (smoking status, ECOG PS, liver metastases, LDH and NLR), were included in the EPSILoN score to validate it in this cohort. Finally, three different survival groups defined as high, intermediate and low for PFS (6.0 vs 3.8 vs 1.9 mo respectively, HR 1.94 95% IC 1.51–2.48, p < 0.001) and OS (24.5 vs 8.9 vs 3.4 months, respectively HR 2.40, 95% IC 1.82–3.17, p < 0.001) were identified.

    fd69c5cf902969e6fb71d043085ddee6 Conclusions
    

    EPSILoN score which combine five baseline clinical and blood biomarkers may help identify patients who most likely will benefit or not from IO in clinical practice in aNSCLC patients treated with second-line IO. Furthermore, it seems to play an important role in both PFS and OS.

    b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
    

    The authors.

    213f68309caaa4ccc14d5f99789640ad Funding
    

    Has not received any funding.

    682889d0a1d3b50267a69346a750433d Disclosure
    

    M.C. Garassino: Consultancies, honoraria: AstraZeneca, Roche, Boehringer Ingelheim, BMS, MSD, Eli Lilly, Novartis, Bayer, Pfizer, Sanofy, Italfarmaco. D. Signorelli: Consultancies, honoraria: AstraZeneca. All other authors have declared no conflicts of interest.

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    188TiP - Metformin &#x0002B;/- cyclic fasting mimicking diet in combination with platinum-pemetrexed chemotherapy for advanced LKB1 inactive lung adenocarcinoma: The FAME trial (ID 497)

    12:30 - 13:00  |  Presenting Author(s): Giulia Galli
    • Abstract
    • Slides

    Background
    

    LKB1 inactive (LKB1i) lung adenocarcinoma (LA) has an aggressive behavior and is resistant to immunotherapy (IO). LKB1i cells are vulnerable to nutrient starvation. Based on preclinical data showing a synergy cisplatin-metformin, we hypothesized that combining platinum-based chemotherapy (CT) with metformin +/- a calorie-restricted, low-carbohydrate, low-protein diet known as Fasting Mimicking Diet (FMD) may improve the efficacy of CT in patients (pts) with LKB1i LA.

    a9ded1e5ce5d75814730bb4caaf49419 Trial design
    

    FAME is a monocentric, open label, double arm, non comparative, randomized, single stage, pick-the-winner phase II trial. Primary objective is Progression Free Survival (PFS), evaluated in comparison with a historical cohort of pts treated with CT. Secondary objectives consist in studying experimental treatment toxicity, response rate, overall survival, metabolic changes in blood, urine and stool, correlation between LKB1 mutation status and LKB1 protein expression. Main inclusion criteria are: advanced LKB1i LA, absence of EGFR mutations and ALK/ROS1 rearrangements, PDL1 expression < 50%, performance status 0-1. Main exclusion criteria are: body mass index <20 kg/m², weight loss ≥5% in the previous 3 months, diabetes mellitus, active brain metastases, baseline fasting glucose ≤65 mg/dL, arterial pO2 <70 mmHg, high blood lactates. Eligible pts will be randomized 1:1 to up to 4 cycles of platinum-pemetrexed CT + metformin, or up to 4 cycles of platinum-pemetrexed CT + metformin + FMD. After 4 cycles, stable/responding pts will continue pemetrexed + metformin until progression or toxicity. Forty-one pts per arm will be necessary to identify a 4.4 mos increase in median PFS. Brookmeyer-Crowley test will be used with an α tail of .15 and a power of .8 mos. Assuming a dropout rate of 5%, the number of pts to enroll will be 88.

    d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification
    

    NCT03709147, first posted on 17 October 2018; EudraCT: 2018-000788-95.

    7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study
    

    Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

    213f68309caaa4ccc14d5f99789640ad Funding
    

    AIRC (Associazione Italiana per la Ricerca sul Cancro) Investigator Grant 2017.

    682889d0a1d3b50267a69346a750433d Disclosure
    

    All authors have declared no conflicts of interest.

    cffcb1a185b2d7d5c44e9dc785b6bb25

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