Virtual Library
Start Your Search
A. Gazzah
Author of
-
+
P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.03b-050 - Prognostic Value of HLA-A2 Status in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 4773)
14:30 - 14:30 | Author(s): A. Gazzah
- 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.
-
+
P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02b-102 - Osimertinib Benefit in ctDNA T790M Positive, EGFR-Mutant NSCLC Patients (ID 5472)
14:30 - 14:30 | Author(s): A. Gazzah
- Abstract
Background:
The third generation tyrosine kinase inhibitors (TKIs) osimertinib is approved for patients with acquired epidermal growth factor receptor (EGFR) T790M mutations in advanced non-small cell lung cancer (NSCLC) patients. New tissue biopsy to detect T790M cannot always be performed, due to the size or location of the lesions and risk of complications to the patient. As an alternative, liquid biopsies based on circulating cell-free tumor DNA (ctDNA) analysis have been described. We assess the efficacy of osimertinib in ctDNA T790M-positive, EGFR-mutant NSCLC patients with progression under first- or second-generation EGFR TKIs ineligible for tissue biopsy at progression; and the feasibility of identifying T790M mutations in ctDNA isolated from blood samples in this cohort of patients.
Methods:
ctDNA analysis using enhanced eTAm-Seq™ assay (Inivata), and enhanced version of the Tam-Seq ® assay was conducted in 48 eligible patients treated in a single center between April 2015 and April 2016. Patients determined to have T790M mutation were prescribed osimertinib (80mg daily). Objective response rate (ORR) by RECIST 1.1 criteria was centrally reviewed and correlated with (A) T790M allele fraction, (B) EGFR activating mutation allele fraction, and (C) T790M by EGFR activating mutation allele fraction ratio.
Results:
T790M status in ctDNA was assessed in 48 EGFR-mutant NSCLC patients. Median age was 65 years (range 37-83); 36 (75%) patients were women and 58% were never-smoker. EGFR mutation status was Del19 in 33 (69%) and L858R in 15 (31%) NSCLC patients. The ctDNA T790M mutation was positive in 24 out of 48 (50%) patients, and 23 out of 24 T790M-positive samples maintained the original activating EGFR mutation in ctDNA analysis. Among evaluable patients (n=16), osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. Neither correlation between ctDNA T790M AF and RECIST radiological response was observed, nor with the other parameters evaluated. Of the seven cases with best response (decrease of 50% or more in size), 3 cases had T790M detected at <0.25%.
Conclusion:
Osimertinib efficacy in a real-world setting among T790M-positive tumours detected in ctDNA from liquid biopsy support the use of such liquid biopsies as a surrogate marker for T790M in tumour tissue, avoiding the need for invasive tumor biopsies for personalising treatment in lung cancer patients
-
+
P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
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 - 14:30 | Author(s): A. Gazzah
- 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.
-
+
P3.02c-066 - HLA-A2 Status and Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 4774)
14:30 - 14:30 | Author(s): A. Gazzah
- 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.
