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Laura Bonanno



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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      158P - Immune-related adverse events (irAEs) in advanced non-small cell lung cancer (aNSCLC): Platelet-to-lymphocyte ratio (PLR) predicts the risk of development and relapse (ID 288)

      12:30 - 13:00  |  Author(s): Laura Bonanno

      • Abstract

      Background

      Immune checkpoint inhibitors (ICIs) have radically changed the treatment of aNSCLC patients (pts). IrAEs are mainly reversible but they require timely recognition and management and may be potentially life-threatening. No predictive markers are available to predict the onset of irAEs and their risk of recurrence. Aim of the study was to evaluate the potential role of circulating markers in predicting the development of irAEs.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      We retrospectively reviewed clinical data of aNSCLC pts consecutively treated with ICIs at Istituto Oncologico Veneto (Padua, Italy) and at San Bortolo General Hospital (Vicenza, Italy) between August 2013 and August 2018. We collected data on the type, grading (G) and timing of irAEs and calculated NLR and PLR before first ICI administration and at the onset of the irAEs. The values were dichotomized for analysis in two groups: high (H-) and low (L-) NLR and H- and L-PLR using pre-identified cut-offs of 3 and 180, respectively.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      The analysis included 194 pts. ICIs were administered as first-line treatment in 29 (15%) pts. Median number of ICIs cycles was 6 (range: 1-66). Median PFS and OS were 4.6 months (m) (95% CI: 3.3-5.9) and 8.7m (95% CI: 6.1-11.4). Seventy-two pts (37%) developed irAEs, mainly G1-2 (68%), with permanent discontinuation of ICI in 23 (32%) cases; 15 pts (20.8%) experienced more than one irAE. Median time to irAE onset was 77 days (7-751 days). Pts with baseline L-NLR and L-PLR values had a higher risk of irAE development (OR = 1.98, 95% CI: 1.09-3.61, p = 0.025 and OR = 2.15, 95% CI: 1.16-3.98, p = 0.016). Multivariate analysis confirmed PLR as independent predictive marker (OR = 2.01, 95%CI: 1.02-3.96; p = 0.045). Among pts who experienced irAE, L-PLR at time of irAE onset was associated with the risk of irAE recurrence or second irAE development (OR = 4.5, 95% CI: 1.11-18.16, p = 0.035).

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Baseline evaluation of NLR and PLR may be a tool to predict the risk of irAE onset and to personalize clinical follow-up during and after treatment with ICIs. The evaluation of PLR at the time of irAE onset might predict the risk of further toxicity. If validated, PLR value may support the clinical decision of re-introducing ICIs after discontinuation.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      Istituto Oncologico Veneto (IOV), Padua, Italy.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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      26P - Potentialities of liquid biopsy in advanced non-small cell lung cancer (aNSCLC): Early evaluation of sentinel mutations in plasma and outcome of patients treated with immunotherapy (ID 504)

      12:30 - 13:00  |  Presenting Author(s): Laura Bonanno

      • Abstract

      Background

      The introduction of immune-checkpoint inhibitors (ICIs) in the management of aNSCLC has led to great outcome improvement, but reliable predictive biomarkers are still a need. Liquid biopsy has the potential to monitor biological effects of treatment. Aim of the study is to explore the potential predictive value of its dynamic analysis in aNSCLC treated with ICIs.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      aNSCLC patients consecutively treated with ICIs at Istituto Oncologico Veneto were prospectively enrolled and genotyped in tissue. Plasma samples were collected at baseline (T1), after three or four weeks according to the administration schedule (T2) and at the moment of the first radiological evaluation (T3). Patients carrying KRAS mutation in tissue were analyzed in plasma with droplet digital PCR (ddPCR). Semiquantitative index of fractional abundancy of mutated allele (MAFA) was used.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      aNSCLC patients (N: 54) were prospectively enrolled and tissue genotyped, 24 of them carried KRAS mutation in tissue and 11 (46%) were positive in plasma at baseline. Positivity was not associated with tumor burden or other clinical features. We evaluated the impact of the presence and the quantitative variation of MAFA during treatment on outcome in terms of progression free-survival (PFS). After a median follow-up of 10.9 months, the presence of sentinel mutation at T1 did not affect PFS, whereas the MAFA increase from baseline to T2 and to T3 were associated with shorter PFS (HR: 5.9, 95%CI: 1.2-27.7, p:0.02 and HR: 12.1, 95%CI: 2.3-23.8, p:0.003, respectively). Median PFS was 5.2 months in the presence of MAFA increase T1-2, while it was not reached in case of decreased/stable MAFA.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Increase in MAFA from baseline to three or four weeks after the start of ICI is associated with shorter PFS. Predictive value of dynamic analysis of sentinel mutations in plasma during ICIs treatment warrants further validation in aNSCLC.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      Istituto Oncologico Veneto.

      213f68309caaa4ccc14d5f99789640ad Funding

      Istituto Oncologico Veneto.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

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