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Attend this session at the
2019 ASCO Annual Meeting!


Session: Lung Cancer—Non-Small Cell Metastatic

Type: Poster Session

Time: Sunday June 2, 8:00 AM to 11:00 AM

Location: Hall A

Whole exome sequencing (WES) of non-small cell lung cancer (NSCLC) for tumor mutational burden (TMB) analysis and long-term benefit to immune checkpoint inhibitors (ICIs).

Sub-category:
Metastatic Non-Small Cell Lung Cancer

Category:
Lung Cancer—Non-Small Cell Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
9071

Poster Board Number:
Poster Session (Board #394)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 9071)

Author(s): Enriqueta Felip, Alejandro Navarro, Ana Callejo, Alex Martinez Marti, Susana Cedres, Nuria Pardo, Javier Ros, Juan David Assaf, Anna Pedrola, Cristina Viaplana, Irene Sansano, Jose Jimenez, Paolo Nuciforo, Miriam Sansó, Rodrigo Dienstmann, Ramon Amat, Francesco M Mancuso, Ana Vivancos; Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Vall d'Hebron University Hospital/Vall d´Hebron Institute Oncolgy (VHIO), Barcelona, Spain; Vall d´Hebron University Hospital /Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain; Vall d’Hebron University Hospital /Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain; Vall D´Hebron University Hospital, Barcelona, Spain; Vall d´Hebron University Hopsital, Barcelona, Spain; Oncology Data Science Group, Vall D’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Oncology Data Science (ODysSey) Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain; Vall d'Hebron University Hospital, Barcelona, Spain; Molecular Pathology Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Molecular Oncology Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Cancer Genomics Group, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain; Oncology Data Science Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Thoracic Cancer Group, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain; Cancer Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Cancer Genomics Lab and Molecular Pathology Lab, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

Abstract Disclosures

Abstract:

Background: ICIs have significantly changed the therapeutic landscape of advanced NSCLC. As such, characterizing predictive markers of long-term clinical benefit is a critical objective. TMB quantification using targeted gene panels associates with long-term response to ICIs in NSCLC patients (Rizvi H ASCO 18). Although TMB quantified by targeted NGS correlates with that of WES, caution may be needed when using smaller panels. Methods: Here we analyzed WES of tumors and matched normal tissue from 67 NSCLC patients including 42 treated with ICIs. We correlated TMB with clinico-pathological features and outcomes. TMB was categorized as high vs. low according to the upper quartile of cohort distribution. Results: The median TMB was 2.68 non-synonymous variants (nSNVs)/Mb, ranging from 0 to 15.6 nSNVs/Mb, with upper quartile at 5.42 nSNVs/Mb. TMB was higher for smoker/current smoker (median 3.51) compared to never smokers (median 0.94, p = 0.0048) but no differences were seen in elderly ( > 70 years) vs. young patients or across histologies (squamous, adeno and other) and stages at diagnosis. In patients treated with ICIs, median TMB was 5.44 for those achieving complete response, 3.87 for patients with partial response and 2.42 for patients with progressive disease (PD) (p = 0.04). Moreover, improved clinical outcomes were associated with higher TMB (Table). In patients treated with ICIs, TMB as continuous variable had an impact on progression free survival (PFS) (p = 0.03). Median PFS was 22.3 months (mo) (14-not reached) for those with high TMB and 6.4 mo (3-16) for those with low TMB (HR 0.34, 0.13-0.9, p = 0.03). Median overall survival was not reached for those patients with high TMB and 32 mo (22-43) for those with low TMB (HR 0.29, 0.1-0.86, p = 0.02). Conclusions: High TMB correlates with long-term ICI benefit in NSCLC patients. Mutations in individual genes potentially linked to long-term benefit or resistance to ICIs will be presented.

TMB in the 4 subgroups based on benefit to ICIs.

ICI benefit< 6 mo
N = 17
6-18 mo
N = 9
> 18 mo and PD
N = 8
> 2 years ongoing
N = 8
p value
Median TMB1.921.614.586.080.04
High TMB5.8%11.1%25%37.5%0.01

 
Other Abstracts in this Sub-Category:

 

1. Association of STK11/LKB1 genomic alterations with lack of benefit from the addition of pembrolizumab to platinum doublet chemotherapy in non-squamous non-small cell lung cancer.

Meeting: 2019 ASCO Annual Meeting Abstract No: 102 First Author: Ferdinandos Skoulidis
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

2. Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

Meeting: 2019 ASCO Annual Meeting Abstract No: 110 First Author: Sean Khozin
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

3. RELAY: A multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 9000 First Author: Kazuhiko Nakagawa
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

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