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Diego Cortinovis
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MA11 - Biomarkers of IO Response (ID 912)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 203 BD
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MA11.05 - Indoleamine 2,3-Dioxygenase Expression in Non-Small-Cell Lung Cancer: Analyses of Prevalence, Clinical Correlations and Prognostic Impact (ID 13309)
11:00 - 11:05 | Author(s): Diego Cortinovis
- Abstract
- Presentation
Background
Indoleamine 2,3-dioxygenase-1 (IDO-1) is a cytosolic enzyme involved in the catabolism of tryptophan; IDO-1-related immune suppression is due to decreased tryptophan availability and to the generation of tryptophan metabolites, culminating in substantial suppression of T-lymphocytes. Here we investigate IDO-1 expression in a cohort of non-small-cell lung cancer (NSCLC) specimens, both in tumor cells and in immune infiltrate, with correlation of IDO-1 to PD-L1 expression, clinical patient demographics and outcomes.
a9ded1e5ce5d75814730bb4caaf49419 Method
A cohort of 1.200 NSCLC samples were obtained from 437 patients who underwent surgical lung resections at Austin Health, Melbourne, Australia. IDO-1 expression was evaluated by immunohistochemistry. Correlations were assessed using Spearman and Kendall tests. A Cox proportional hazards (PH) model was used to assess if overall survival (OS) was associated with IDO-1 positivity in univariate and multivariable settings.
4c3880bb027f159e801041b1021e88e8 Result
Samples from 437 patients were analyzed for IDO-1 expression, with 111 (25.4%) determined as positive (H-Score ≥ 1) and 326 patients (74.6%) as negative (H-Score: 0). IDO-1 expression was determined to be greater in tumor immune infiltrate, with 406 patients (93.8%) determined as positive, while just 27 (6.2%) were IDO-1 negative. There was a significant positive correlation between IDO-1 positive tumor cells and immune cells (0.2167, p < 0.001). Both continuous and binary versions of tumor H-Score showed a significant positive correlation with the amount of tumor immune infiltrate (0.1806 and 0.1698, p < 0.0001, respectively). None of the analyzed variables (age, sex, histology, stage, EGFR, KRAS and PD-L1 status) were found to display a significant correlation with IDO-1 positivity in tumor and immune cells. IDO-1 positivity in tumor cells was found to be significantly associated with OS in the univariate setting and in the multivariable model where variables age, sex, histology, stage, EGFR, KRAS and PD-L1 status were included [P-value = 0.009 and 0.021, respectively; HR: 0.72 (95% CI: 0.55-0.95)]. IDO-1 positivity in immune cells was found to be significantly associated with OS in the univariate setting and was borderline significant in the multivariable model [P-value = 0.006 and 0.053, respectively; HR: 0.798 (95% CI: 0.635-1.003)].
8eea62084ca7e541d918e823422bd82e Conclusion
To our knowledge, this is the most extensive analysis of IDO-1 expression in NSCLC patients reported in the literature. Our results suggest the possible prognostic role of IDO-1 expression in tumor and immune cells, highlighting the relevance of IDO-1 detection in tumor tissue. Since new compounds targeting IDO-1 are actually under investigation, the identification of potential prognostic and predictive biomarkers will be needed.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA26 - New Therapies and Emerging Data in ALK, EGFR and ROS1 (ID 930)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 201 BD
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MA26.02 - Upfront or Sequential Strategy for New Generation Anaplastic Lymphoma Kinase (ALK) Inhibitors: An Italian Retrospective Study. (ID 12790)
13:35 - 13:40 | Author(s): Diego Cortinovis
- Abstract
- Presentation
Background
Anaplastic lymphoma kinase (ALK) rearrangement confers sensitivity to ALK inhibitors (ALKis) in non-small-cell lung cancer (NSCLC). Although several drugs provided an impressive outcome benefit, the most effective sequential strategy is still unknown.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively collected 242 ALK-positive advanced NSCLC diagnosed between 2010 and 2018 in 23 Italian institutions (expanded data collection from Gobbini et al. Lung Cancer 2017). 138 patients received exclusively crizotinib as ALKi (not considered for this analysis). 78 patients received crizotinib and a new (second or third) generation ALKis as further treatments (group A). 26 patients performed a new generation ALKi as upfront agent (group B). These groups are larger than those considered in a previous analysis (15 and 8 patients, respectively).
4c3880bb027f159e801041b1021e88e8 Result
Study population clinical features and treatments received are summarized in Table 1.
Group A
Crizotinib followed by new generation ALKis
N= 78
Group B
Upfront new generation ALKis
N=26
Treatments per line n(%)
1°
2°
3°
4°
1°
2°
3°
4°
Crizotinib
28(36)
50(64)
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2(8)
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Alectinib
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11(14)
18(23)
5(17)
7(27)
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Ceritinib
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9(12)
23(30)
3(4)
8(31)
8(31)
1(4)
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Brigatinib
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6(8)
6(8)
2(3)
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2(8)
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2(8)
Lorlatinib
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4(5)
5(6)
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1(4)
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Chemotherapy
50(64)
2(3)
10(13)
na
11(42)
6(23)
1(4)
Na
Clinical features n(%)
Age (range)
58 (27-83)
55 (24-82)
Male
37(47)
10(38)
p= 0.42
Female
41(53)
16(62)
Current smoker
8(10)
5(19)
p= 0.23
Never/former smoker
70(90)
21(81)
ALKi beyond PD
27(34)
4(15)
p= 0.06
With a median follow-up of 22.6 months (CI 95% 20.09-25.10), 33 patients had died (32%). In group B, the median progression free survival (PFS) for new generation ALKis administered as first (14.0 months, CI 95% 9.52-18.471), second (12.7 months, CI95% 7.22-18.17) or third-line (12.8 months, CI95% 6.24-19.35) was not statistically different (p= 0.522). The median time from the start of crizotinib to the disease progression after the new generation ALKi sequentially performed (group A) was longer than that one detected in group B for the upfront new generation ALKis (29 vs 14 months, HR 2.47 [CI95% 1.35-4.50], p=0.003). This result was confirmed even considering the time lost between the two treatments in group A. The median overall survival (OS) was not reached. The 12-months OS rate was 97% in group A and 84% in group B.
8eea62084ca7e541d918e823422bd82e Conclusion
New generation ALKis maintain their efficacy regardless of the treatment setting considered. The sequential strategy seems to provide a substantial benefit, but a longer follow-up and larger samples are needed to clarify the survival impact.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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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): Diego Cortinovis
- 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.
6f8b794f3246b0c1e1780bb4d4d5dc53
