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Domenico Galetta
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-15 - ROS1-Rearranged Non-Small Cell Lung Cancer Is Associated with High Rate of Venous Thromboembolism: Analysis of The METROS Trial (ID 12287)
16:45 - 18:00 | Author(s): Domenico Galetta
- Abstract
Background
Patients with lung cancer are at increased risk for venous thromboembolism (VTE) and 8% to 15% of patients with advanced non-small-cell lung cancer (NSCLC) experience a VTE event during the course of their disease. The incidence of VTE in molecularly defined NSCLC is still unknown. However, emerging data suggests that patients harbouring ALKrearrangements are at increased risk of VTE. In light of the high amino-acid sequence and structural homology with ALK protein, we undertook this study to determine the incidence of VTE in patients with ROS1-rearranged NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
The METROS trial is a multicentre prospective phase II study designed to assess efficacy, safety and tolerability of Crizotinib in pre-treated metastatic NSCLC with METamplification or METexon 14 mutation or ROS1rearrangement. ROS1-rearranged patients enrolled within cohort A and expansion cohort of the trial were evaluated in this analysis.
4c3880bb027f159e801041b1021e88e8 Result
Among 48 patients with ROS1-rearranged lung adenocarcinomas (median [range] age 50 [28-82]); 17 males [35.4%] and 31 females [64.5%]; PS 0-1 [95.8%], 2 [4.2%]; 21 current/former smokers [43.75], 27 never smokers [56.25]) , 20 (41.6%) had at least one VTE event. VTE events consisted in pulmonary embolism (PE) in 11 patients (55%), deep vein thrombosis (DVT) in 11 patients (55%), renal vein thrombosis in 2 patients (10%). Seven patients (35%) had ≥ 1 VTE event. Patients with VTE were more likely to be older than 65 years (P = 0.029). No other associations between clinical characteristics and development of VTE were observed. The occurrence of VTE was not associated with overall survival.
8eea62084ca7e541d918e823422bd82e Conclusion
The incidence of VET is 3- to 5-fold higher in patients harbouring ROS1-rearrangment than previously observed for the general NSCLC population. Whether molecular profile of NSCLC should be incorporated into a risk-stratification tool and decision-making algorithm for VTE diagnosis, prophylaxis and treatment remains to be determined prospectively.
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P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.04-12 - Prognostic and Predictive Role of Peripheral Blood Biomarkers in NSCLC Patients Treated with Checkpoint, a Single-Center Experience. (ID 14004)
12:00 - 13:30 | Presenting Author(s): Domenico Galetta
- Abstract
Background
Tumor characteristics and host immune system play a crucial role for the immune response. As reported in preclinical studies, a sustain immune cell proliferation in the periphery is necessary for the immune response and tumor destruction. More evidence in melanoma patients (pts) and less evidence are available in non small cell lung cancer (NSCLC). Aim of this study is to demonstrate the role of the peripheral blood as biomarkers in NSCLC patients treated with checkpoint inhibitors (CPIs).
a9ded1e5ce5d75814730bb4caaf49419 Method
94 evaluable patients from one institution NSCLC pts, treated with at least one course immunotherapy (IO) (nivolumab and pembrolizumab) in 2nd or further line, were considered for analysis. Baseline peripheral blood, at week 2 and 4 were collected for each patients. Univariate analysis were performed and correlation between biomarkers and progression free-survival (PFS) and overall survival (OS) are reported.
4c3880bb027f159e801041b1021e88e8 Result
median age was 67 years (31-86 years), most pts were male (80%), 35 pts were S and 59 NS. 75,5% of pts were smokers and Eastern Cooperative Oncology Group (ECOG) pre-IO were: 0 (5,3%), 1 (58,5%) and 2 (36,2%). Overall median (m) PFS and mOS were 3,93 months (mo) and 20,7 mo respectively. Baseline absolute neutrophil count (ANC) ≥ 7500/µL and neutrophil to lymphocyte ratio (NLR) >5 correlate with worse PFS (3.3 mo vs 5.5 mo, p=0.04 and 2.8 mo vs 5.4 mo, p=0.006 respectively) and OS ( 15.6 mo vs 34.9 mo p=0.02 and 16.7 vs 34.9 mo p=0.004, respectively ). Poor OS and PFS were persist at week 2 in pts with NLR ≥5 (HR=0.3, p<0.0001 for OS and PFS), this was not significant at week 4. Also, baseline derived neutrophil to lymphocyte ratio (dNLR) >3 correlate with worse PFS ( p=0.01) and OS (p=0.016). Absolute lymphocyte count (ALC) ≥1000/µL at baseline and week 2 confer higher PFS (5.3 mo vs 3.1 mo, p=0.05) and a tred in OS. Interestingly, week-4 absolute monocytic count (AMC)≥ 1000/µL imply a poor PFS and this was not observed at baseline and week 2. Low, absolute eosinophil count (AEC) <50/ µL correlate with worse PFS (p=0.031). Finally, pts with lymphocyte monocyte ratio (LMR)≥ 1.5 at baseline, week 2 and 4 correlate with better survival.
Table. 1 Univariate analysis of peripheral blood biomarker and survival outcome in NSCLC patients treated with immunotherapy
Biomarker
Outcome
Survival
(months)
Impact
(HR CI95%, p-value)
Results
Baseline
ANC≥ 7500/µL
OS
15.6 mo vs 34.9 mo
HR= 0.43, p=0.002
Poor OS
Poor PFS
PFS
3.3 mo vs 5.5 mo
HR= 0.61, p=0.04
Baseline
NLR ≥ 5
OS
16.7 mo vs 34.9 mo
HR=0.45, p=0.004
Poor OS
Poor PFS
PFS
2.8 mo vs 5.4 mo
HR=0.50, p=0.006
2 weeks
NLR≥ 5
OS
11.9 mo vs 35 mo
HR=0.32, p<0.0001
Poor OS
Poor PFS
PFS
2.6 mo vs 6.1 mo
HR=0.31, p<0.0001
Baseline
dNLR> 3
OS
16.7 mo vs 34.8 mo
HR= 0.51, p=0.016
Poor OS
Poor PFS
PFS
2.8 mo vs 5.4 mo
HR= 0.52, p= 0.01
Baseline
ALC≥ 1000/µL
OS
31.7 mo vs 26.4 mo
HR=1.23, p=0.54
Same OS
Good PFS
PFS
5.3 mo vs 3.1 mo
HR= 1.8, p=0.05
2 weeks
ALC≥ 1000/µL
OS
34.8 vs 18 mo
HR=1.4, p=0.14
Same OS
Good PFS
PFS
8.1 mo vs 3.3 mo
HR=1.8 , p=0.007
4 weeks
AMC≥ 1000/ µL
OS
34.8 mo vs 31.7 mo
HR=1.0, p=0.91
Same OS
Poor PFS
PFS
3.3 mo vs 8.0 mo
HR=0.43, p=0.003
Baseline
LMR≥ 1.5
OS
34.8 mo vs 15.0 mo
HR=2.1, p=0.007
Good OS
Good PFS
PFS
5.3 mo vs 2.6 mo
HR=1.8, p=0.025
2 weeks
LMR≥ 1.5
OS
34.9 mo vs 15.0 mo
HR=1.92, p=0.025
Good OS
Good PFS
PFS
6.1 mo vs 2.8 mo
HR=3.4, p<0.001
4 weeks
LMR≥ 1.5
OS
35.1 mo vs 16.7 mo
HR=2.7, p=0.003
Good OS
Good PFS
PFS
5.9 mo vs 3 mo
HR=2, p=0.017
Baseline
(AEC) <50/ µL
OS
26.4 mo vs 24.6 mo
HR=0.83, p=0.55
Same OS
Poor PFS
PFS
3.4 mo vs 5.6 mo
HR=0.55, p=0.034
NSCLC non-small cell lung cancer, ALC absolute lymphocyte count, ANC absolute neutrophil count, NLR neutrophil to lymphocyte ratio, dNLR absolute neutrophil count/(white blood cell count-absolute neutrophil count), AEC absolute eosinophil count, AMC absolute monocyte count, LMR lymphocyte monocyte count, OS overall survival, PFS progression free survival, RR response rate, HR hazard ratio,
8eea62084ca7e541d918e823422bd82e Conclusion
Despite the retrospective nature, in our knowledge, this is the first study to demonstrate the role of AMC in NSCLC pts. Also, LMR could probably reflect the peripheral immune-fitness. However, prospective sudies are needed to confirm their role.
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