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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

Tracking plasma KRAS mutations (mu) in lung adenocarcinoma (LUAC) patients (p) and branching evolution.

Sub-category:
Metastatic Non-Small Cell Lung Cancer

Category:
Lung Cancer—Non-Small Cell Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
9055

Poster Board Number:
Poster Session (Board #378)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 9055)

Author(s): Jillian Bracht, Niki Karachaliou, Richard B. Lanman, Daniel Dix, Iris Faull, Rebecca Nagy, Noemí López, Ramon Palmero, Santiago Viteri Ramirez, Margarita Majem, Alvaro Taus, Enric Carcereny Costa, Javier Garde, Francois Riva, Andrea Malfettone, Miguel Sampayo, Ana Drozdowskyj, Enriqueta Felip, Rafael Rosell; Pangaea Oncology, IOR, Quirón-Dexeus University Institute, Laboratory of Cellular and Molecular Biology, Barcelona, Spain; University Hospital Sagrat Cor, Barcelona, Spain; Guardant Health, Inc., Redwood City, CA; Guardant Health, Redwood City, CA; Medsir-Medica Scientia Innovation Research, Barcelona, Spain; Department of Medical Oncology, Catalan Institute of Oncology, Hospitalet (Barcelona), Spain; Dexeus University Hospital, Quiron Salud Group, Barcelona, Spain; Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Hospital del Mar, Barcelona, Spain; Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain; MedSIR- Medica Scientia Innovation Research, Barcelona, Spain; MedSIR - Medica Scientia Innovation Research, Barcelona, Spain; Health Sciences Research Institute of the Germans Trias i Pujol Foundation (IGTP), Badalona, Barcelona, Spain; Lung Cancer Unit, Hospital Universitari Vall d'Hebron and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain and Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain and Institute of Oncology Rosell (IOR), University Hospital Sagrat Cor, Badalona, Barcelona, Spain

Abstract Disclosures

Abstract:

Background: KRAS m in LUAC p are recalcitrant to therapy. In mice models and p, STK11 m confer poor prognosis. Patients with KRAS, or KRAS with TP53 m, benefit from immunotherapy (IO). We used a cell free DNA (cfDNA) sequencing platform to sub-group 53 LUAC p with KRAS m from the Spanish Lung Liquid versus Invasive biopsy Program (SLLIP, NCT03248089), according to the coexistence of TP53 and STK11 m. We evaluated the treatment outcome in the KRAS subgroups and we explored the mutational evolution at 2 weeks (w), and at the end of the study (EOS). Methods: SLLIP was a multi-center observational study in patients with treatment-naïve metastatic LUAC. Genotyping, with a clinically validated cfDNA assay (Guardant360) was performed at 3 time points: before start of treatment, at 2 w, and upon progression or at 12 months (mo). Oncoprints were constructed based on mutation status and variant allele frequency (VAF). Results: 53 p with KRAS alterations were included. 36 male; median age 59; 46 current/ex-smokers; 64% received 1st line platinum-based chemotherapy (CT), 4% platinum-based CT+IO, 8% platinum-based CT plus bevacizumab, and 24% other or no therapy. 13 p had only KRAS m (K-only group), 25 p had KRAS + TP53 m (KP group), and 15 p had KRAS + STK11 with or without TP53 m (KS group). Median progression-free survival was 3.5 mo for all 53 p, 4.8 mo for the K-only group, 4.4 mo for the KP group, and only 2.6 mo for the KS group (p = 0.05 for KS versus K-only). The average VAF for K-only, KP, and KS groups at EOS were 6.4%, 9.7%, and 46%, respectively. When looking at p with cfDNA analysis at the three time points, the following were observed: In the K-only group, 25% lost KRAS m at 2 w and 50% at EOS. 50% and 75% gained TP53 m, at 2 w and EOS, respectively. None gained STK11 at the 2 time points. In the KP group, 40% lost KRAS m at 2 w but all had KRAS m at EOS. 20% and 10% lost TP53 m, at 2 w and EOS, respectively. 10% gained STK11 m at the 2 time points. In the KS group, 33% lost KRAS m at the 2 time points. All and 33% lost STK11 m at 2 w and EOS, respectively. 66% gained TP53 at the 2 time points. Conclusions: Subgroups of KRAS m traced in cfDNA confirm dismal prognosis to 1st line therapies. These findings prompt us to tailor IO for K-only or KP subgroups. For p with STK11 m, restoration of the STK11 function is warranted. Clinical trial information: NCT03248089

 
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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