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L. Mezquita



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    P1.01 - Poster Session with Presenters Present (ID 453)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Epidemiology/Tobacco Control and Cessation/Prevention
    • Presentations: 1
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      P1.01-004 - Is There Any Role of Residential Radon in Non Small Cell Lung Cancer (NSCLC) Patients Harboring Molecular Alterations? (ID 4770)

      14:30 - 15:45  |  Author(s): L. Mezquita

      • Abstract

      Background:
      Radon gas is the first cause of lung cancer in non-smoking population. The World Health Organization (WHO) recommends radon concentration lower than 100 Bq/m3. In recent years, most of the advances in personalized therapy in NSCLC patients also occurred in non-smokers. Furthermore, limited information is available about the clinical and pathological characteristics in patients exposed to radon gas. We hypothesized that residential radon could be associated to some specific pathological and molecular alterations in NSCLC patients.

      Methods:
      Prospective study of a cohort of NSCLC patients harbouring molecular alterations (EGFR, BRAF mutations (m), ALK and ROS1 rearrangements (r)) in our centre, between September 2014 and October 2015. A radon detector alpha-track was given to each patient to measure residential radon concentration for 3 months; it was analysed using optical microscopy. We collected demographic information, smoking history, environmental exposure and clinical characteristics. The pathologic characteristics were prospectively revised by a lung cancer pathologist, including histology pattern, grade and inflammatory infiltrate. EGFR and BRAF mutation (m) were analyzed using quantitative real-time polymerase chain reaction (PCR) and ALK and ROS1 rearrangement by fluorescence in situ hybridization (FISH). Data was analyzed using IBM SPSS v.20.

      Results:
      60 detectors were delivered (10% missing), 48 patients were evaluated (89.6% living in Madrid). Median age 66.5 (29- 82); 33 (68.8%) females; 33 non-smokers (31.3% passive smokers and 35.4% childhood exposure) and 3 (6.3%) light smokers. 100% adenocarcinoma (35.4% mixte, 18.8% acinar, 10.4% solid, 8.3% papillary, 8.3% micropapilllary, 8.4% others and 10.4% unknown); EGFRm 36 patients, ALKr 10 patients and BRAFm 2 patients. Home characteristics measured: 79.2% flat (89.1% measurement at bedroom); building material: 89.6% bricks. Median length of stay was 28 years (2-55). Median height of house 2 floors (0-15). Median of radon concentration: 104 Bq/m3 (42- 915); 60.42% over WHO recommendation. By molecular alteration: EGFRm median 96 Bq/m3 (42-915), ALKr median 116 (64-852) and BRAFm median 125 (125). A significant association was observed between non-EGFR mutation and concentration over the WHO recommendation (p=0.044). In univariant analysis, radon concentration was associated with non-mucinous histology and low tumoral grade (p=0.033 and p=0.023, respectively).

      Conclusion:
      Our final results have shown no consistent association between residential radon and molecular alterations in NSCLC patients, but a trend has been suggested in ALKr and BRAFm. Large multicenter studies are needed to confirm this hypothesis.

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    P2.03b - Poster Session with Presenters Present (ID 465)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.03b-050 - Prognostic Value of HLA-A2 Status in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 4773)

      14:30 - 15:45  |  Author(s): L. Mezquita

      • Abstract

      Background:
      The class I human leucocyte antigen (HLA) molecules play a critical role as escape mechanism of antitumoral immunity. Indeed, novel immune-targeting cancer vaccines are currently developped in HLA-A2 positive patients for modulating the T cells response. The HLA-A2 status has been proposed as prognostic factor in lung cancer, but previous evidence is inconsistent. The aim of this study is to evaluate the role of HLA-A2 status as prognostic factor in a large cohort of advanced NSCLC patients.

      Methods:
      Advanced NSCLC patients eligible to platinum based chemotherapy (CT) were included from Oct. 2009 to July 2015 in the prospective MSN study (IDRCB A2008-A00373-52) in our institute. HLA-A2 status was analysed by flow cytometry. Clinical and pathological data were collected in a Case Report Form (CRF). Statistical analysis was performed with software SAS version 9.3.

      Results:
      Five hundred forty-five advanced NSCLC patients were included. Three hundred forty-four patients (63%) were male, median age was 61 years (21-84); 466 (85%) were smokers. Four hundred seven (75%) were adenocarcinoma, 69 (13%) squamous and 69 (13%) others histologies. Among 259 patients with known molecular profile, 113 (43.6%) NSCLC were KRASmut, 50 (19.3%) EGFRmut, 30 (11.6%) ALK positive, 9 (3.5%) BRAFmut and 8 (3.1%) FGFR1amp. Four hundred forty-seven (83%) patients had performance status 0-1 at diagnosis. Five hundred eight patients (93%) were stage IV, and 37 (7%) stage IIIB. All received platinum-based CT (49% cisplatine, 42% carboplatin and 9% both). No association was observed between HLA-A2 status and patient or tumor characteristics. The median progression free survival to platinum-based CT (PFS) was 5.6 months [confidence interval (CI) 95% 5.20-6.10]. In HLA-A2 positive patients, the median PFS was 5.6 months [CI 95% 5.1-6.4] vs. 5.7 months [CI 95% 4.9-6.2] in HLA-A2 negative patients (HR 1, Wald test, p=0.8).The median overall survival (OS) was 12.6 months [CI 95% 11.3-14.3]. The median OS was 12.8 months [CI 95% 11-14.6] in HLA-A2 positive vs. 12.5 months [CI 95% 10.4- 15.3] in HLA-A2 negative patients (HR 1, Wald test p=0.61). No significant differences were found between HLA-A2 status and PFS and OS in advanced NSCLC patients.

      Conclusion:
      Our study has observed no prognostic role of HLA-A2 status in advanced NSCLC patients.

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    P3.02c - Poster Session with Presenters Present (ID 472)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 3
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      P3.02c-031 - Immune Checkpoint Inhibitors (IC) and Paradoxical Progressive Disease (PPD) in a Subset of Non-Small Cell Lung Cancer (NSCLC) Patients (ID 5448)

      14:30 - 15:45  |  Author(s): L. Mezquita

      • Abstract

      Background:
      In non-squamous NSCLC PD-L1 negative patients (pts), IC might increase the risk of early death compared to docetaxel in the phase III study Checkmate 057. Tumor Growth Rate (TGR) is calculated using 2 CTscans and the time interval between the 2 exams. It integrates tumor dynamics and kinetics. We hypothesized that TGR could identify a subset of pts named PPD, in which IC could accelerate tumor progression, leading to early death.

      Methods:
      We performed a retrospective case study of all NSCLC pts treated by IC in a single institution between Dec. 12 and Feb. 16. CT scan were centrally reviewed by a senior radiologist and assessed according to RECIST 1.1 criteria. We calculated TGR at baseline of IC (baseline CTscan (n) vs n-1 CTscan) and TGR during IC (n+2 CTscan vs n+1 CTscan). We further estimated the difference (deltaTGR) between TGR during IC and TGR at baseline. DeltaTGR>0 means IC speeds up tumor growth. PPD was defined as deltaTGR>50%, corresponding to an absolute increase in TGR greater than 50% per month. PDL1 expression was assessed with the SP142 clone.

      Results:
      89 pts were eligible. 58% were male, median age 60 (41-78); 15% never smokers. 62 pts had adenocarcinoma, 21 squamous and 6 other histologies. Mutational status was unknown for 14 pts; 36% wild type, 9 pts EGFRmut, 25 pts KRASmut. PDL1 expression was positive in 25 pts, unknown in 57 pts. 52 pts (58%) received nivolumab, 25 pembrolizumab and 12 atezolizumab. Treatement was received as 1-3[rd] line in 52 pts, and as ≥ 4[th] line in 37 pts. Overall, 25 pts (28%) had a response according to RECIST 1.1 criteria, 31 (35%) a stable disease. Median OS was 14.7 months. During IC, deltaTGR was <0 in 79 pts and >0 in 20 pts. Among the 20 pts with deltaTGR>0, 9 had a PPD. Characteristics (age, sex, smoking status, pathology, number of previous line, PDL1 status) of the 9 pts were not different from other pts. None of the PPD were pseudoprogression. Median OS of PPD vs others was 3.2 and 23 months, respectively. PPD was not more frequent in tumors with high baseline TGR.

      Conclusion:
      Our results suggest that PPD is a new subset of response criteria in which IC may increase tumor progression, leading to a poorer survival. Rapidly growing disease at study entry nor RECIST criteria could predict the occurrence of PPD.

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      P3.02c-065 - Neutrophil-To-Lymphocyte and Other Ratios as Prognostic and Predictive Markers of Immune Checkpoint Inhibitors in Advanced NSCLC Patients (ID 4775)

      14:30 - 15:45  |  Author(s): L. Mezquita

      • Abstract

      Background:
      The inflammatory status in advanced cancer patients before treatment have been asocciated with poor prognosis. Recently, neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) have been proposed to mesure the inflammatory status at diagnosis. However their prognostic/predictive value for immune checkpoint inhibitors is unknown. The aim of this study is to evaluate the role of these parametres to predict outcomes to immune checkpoint inhibitors in NSCLC patients.

      Methods:
      We conducted a retrospective study of a cohort of advanced NSCLC patients (pts) treated with immune checkpoint inhibitors (nivolumab (nivo), pembrolizumab (pembro) or atezolizumab (atezo)) from Nov. 2013 to July 2016 in our institute. Clinical data were collected and complete blood count, lactate dehydrogenase (LDH), and albumin were also collected at baseline and at 2[nd] cycle (after 14 days in case of nivo and after 21 days for pembro and atezo) for monitoring the blood cells counts and the ratios. A statistical analysis was performed with R studio software.

      Results:
      65 NSCLC patients were included. Twenty-five patients (38%) were female, median age was 65 years (30-86); 55/65 patients were current/former smokers and 9 (14%) non-smokers; 50 patients (76%) had performance status 1. Forty-two (64.6%) had an adenocarcinoma, seventeen (26%) squamous cell carcinoma, three (5%) large cells, and three others histologies. Fifty-seven patients (88%) had stage IV (25% had M1a, 75% M1b), and eight (12%) locally advanced disease. The median of immunotherapy line was 2 (2-9). Seventeen patients (26%) received another line of treatment after immunotherapy. Absolut leucocyte count (WBC) and absolut neutrophil count (ANC) at immunotherapy beginning (baseline) were correlated with prognosis (p<0.0001 and p<0.0001). NLR, dNLR [ANC/(WBC-ANC)] and PLR were significantly correlated with survival from immunotherapy beginning (p<0.001, p=0.021 and p=0.003, respectively). An early increase of NLR and dNLR at 2[nd] cycle were prognostic for shorter survival (p<0.0001 and p=0.0011). Increases of ANC and absolut eosinophils count (AEC), and decreases of absolut lymphocytes count (ALC) at 2[nd] cycle were also associated with poor prognosis (p=0.002, p=0.002 and p=0.048 respectively). Lactate dehydrogenase (LDH) and albumin at baseline were significant prognostic factors to immunotherapy (p<0.0001 and p=0.001).

      Conclusion:
      Our preliminary results suggest that “low cost” and routine blood markers and their early changes could be associated with outcomes to immunotherapy in advanced NSCLC. A multivariate analysis on 130 patients will be presented.

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      P3.02c-066 - HLA-A2 Status and Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 4774)

      14:30 - 15:45  |  Author(s): L. Mezquita

      • Abstract

      Background:
      The class I human leucocyte antigen (HLA) molecules play a critical role in tumor recognition by T cells and the loss of expression seems to be an escape mechanism of antitumoral immunity. Novel immune-targeting cancer vaccines are currently developped in HLA-A2 positive patients for modulating the T cells immune response. We hypothesized that HLA-A2 status could influence the prognosis and response to immune checkpoints (IC) inhibitors.

      Methods:
      Advanced NSCLC patients treated with nivolumab or within clinical trials (with pembrolizumab or atezolizumab) were prospectively included from November 2013 to July 2016 in our institute. HLA-A2 status was analysed by flow cytometry; PDL1 was analysed by immunohistochemistry. Clinical and biological data were collected at baseline and after cycle 1. Statistical analysis was performed with R studio.

      Results:
      Out of 160 patients treated, HLA-A2 status was available for 65 patients. 40 patients (61.54%) were male, median age was 65 years (30-86); 55 (84.6%) were smokers and 57 (72.3%) had performance status 0-1. 42 patients (64.6%) had an adenocarcinoma, 17 (26.1%) squamous cell carcinoma and 6 (9.2%) others histologies. Molecular status was available in 55 patients: 6 (10.9%) were EGFRmut, 3 (5.4%) ALK positive, 13 (23.6%) KRASmut, 3 (5.4%) BRAFmut and 12 (21.8%) wildtype. PDL1 expression was positive in 13 patients (20%), negative in 5 (7.7%) and unknown in 47 (72.3%). The median of previous lines of treatment was 1 (1-8). HLA-A2 status was positive in 32 patients (49.23%) and negative in 33 (50.76%). HLA-A2 positivity was associated with higher number of metastases at baseline and the presence of liver metastasis (p=0.04 and p= 0.016, respectively). Other patient and tumor characteristics were well balanced between HLA-A2 + and - groups. The median progression free survival to immunotherapy (iPFS) was 4 months [0-40]. In HLA-A2 positive the median iPFS was 4 months vs 4 months in HLA-A2 negative (p=0.63). The median overall survival (OS) was 21 months [0-121]. The median OS was 18.5 months in HLA positive vs. 24 months in HLA-A2 negative patients (p=0.25). No significant difference between both HLA-A2 groups was identified.

      Conclusion:
      Our preliminary results suggest that HLA-A2 status has no predictive or prognostic value in NSCLC patients treated with immune checkpoint inhibitors. An updated analysis on 78 patients will be presented.