Real world outcomes in KRAS G12C mutation positive non-small cell lung cancer

Wanyuan Cui; Fanny Franchini; Marliese Alexander; Ann Officer; Hui Li Wong; Maarten IJzerman; Jayesh Desai; Benjamin J. Solomon

doi:10.1016/j.lungcan.2020.06.030

Real world outcomes in KRAS G12C mutation positive non-small cell lung cancer

Wanyuan Cui^*
, Fanny Franchini
, Marliese Alexander
, Ann Officer
, Hui Li Wong
, Maarten IJzerman
, Jayesh Desai
, Benjamin J. Solomon

^*Corresponding author for this work

Peter Maccallum Cancer Centre
University of Melbourne
Walter and Eliza Hall Institute of Medical Research

Research output: Contribution to journal › Article › Academic › peer-review

70 Citations (Scopus)

540 Downloads (Pure)

Abstract

Background: KRAS mutations are found in 20–30 % of non-small cell lung cancers (NSCLC) and were traditionally considered undruggable. KRAS^G12C mutation confers sensitivity to KRAS^G12C covalent inhibitors, however its prognostic impact remains unclear. This study assesses the frequency, clinical features, prevalence of brain metastases and outcomes in KRAS^G12C NSCLC in a real-world setting. Methods: Patients enrolled in the prospective Thoracic Malignancies Cohort (TMC) between July 2012 to October 2019 with recurrent/metastatic non-squamous NSCLC, available KRAS results, and without EGFR/ALK/ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival (OS) was compared for KRAS wildtype (KRAS^WT) and KRAS mutated (KRAS^mut); and KRAS^G12C and other (KRAS^other) mutations. Results: Of 1386 NSCLC patients, 1040 were excluded: non-metastatic/recurrent (526); unknown KRAS status (356); ALK/EGFR/ROS1 positive (154); duplicate (4). Of 346 patients analysed, 144 (42 %) were KRAS^mut, of whom 65 (45 %) were KRAS^G12C. All patients with KRAS^G12C were active or ex-smokers, compared to 92 % of KRAS^other and 83 % of KRAS^WT. The prevalence of brain metastases during follow-up was similar between KRAS^mut and KRAS^WT (33 % vs 40 %, p = 0.17), and KRAS^G12C and KRAS^other (40 % vs 41 %, p = 0.74). The proportion of patients receiving one or multiple lines of systemic therapy was comparable. OS was similar between KRAS^mut and KRAS^WT (p = 0.54), and KRAS^G12C and KRAS^other (p = 0.39). Conclusion: Patients with KRAS^mut and KRAS^WT, and KRAS^G12C and KRAS^other NSCLC have comparable clinical features, treatment and survival. While not prognostic, KRAS^G12C may be an important predictive biomarker as promising KRAS^G12C covalent inhibitors continue to be developed.

Original language	English
Pages (from-to)	310-317
Number of pages	8
Journal	Lung Cancer
Volume	146
DOIs	https://doi.org/10.1016/j.lungcan.2020.06.030
Publication status	Published - 1 Aug 2020

Bibliographical note

Funding Information:
JD has served as a consultant for Beigene, Lilly, Eisai, Amgen and Biocon; and institution has received research funding from Roche, Lilly, AstraZeneca/MedImmune, Beigene, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Bionomics.

Publisher Copyright:
© 2020

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Real world outcomes in KRAS G12C mutation positive non-small cell lungFinal published version, 3.29 MBLicence: CC BY

Cite this

@article{b2cd4200d68047899c5a9e18e5ea084f,

title = "Real world outcomes in KRAS G12C mutation positive non-small cell lung cancer",

abstract = "Background: KRAS mutations are found in 20–30 \% of non-small cell lung cancers (NSCLC) and were traditionally considered undruggable. KRASG12C mutation confers sensitivity to KRASG12C covalent inhibitors, however its prognostic impact remains unclear. This study assesses the frequency, clinical features, prevalence of brain metastases and outcomes in KRASG12C NSCLC in a real-world setting. Methods: Patients enrolled in the prospective Thoracic Malignancies Cohort (TMC) between July 2012 to October 2019 with recurrent/metastatic non-squamous NSCLC, available KRAS results, and without EGFR/ALK/ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival (OS) was compared for KRAS wildtype (KRASWT) and KRAS mutated (KRASmut); and KRASG12C and other (KRASother) mutations. Results: Of 1386 NSCLC patients, 1040 were excluded: non-metastatic/recurrent (526); unknown KRAS status (356); ALK/EGFR/ROS1 positive (154); duplicate (4). Of 346 patients analysed, 144 (42 \%) were KRASmut, of whom 65 (45 \%) were KRASG12C. All patients with KRASG12C were active or ex-smokers, compared to 92 \% of KRASother and 83 \% of KRASWT. The prevalence of brain metastases during follow-up was similar between KRASmut and KRASWT (33 \% vs 40 \%, p = 0.17), and KRASG12C and KRASother (40 \% vs 41 \%, p = 0.74). The proportion of patients receiving one or multiple lines of systemic therapy was comparable. OS was similar between KRASmut and KRASWT (p = 0.54), and KRASG12C and KRASother (p = 0.39). Conclusion: Patients with KRASmut and KRASWT, and KRASG12C and KRASother NSCLC have comparable clinical features, treatment and survival. While not prognostic, KRASG12C may be an important predictive biomarker as promising KRASG12C covalent inhibitors continue to be developed.",

author = "Wanyuan Cui and Fanny Franchini and Marliese Alexander and Ann Officer and Wong, \{Hui Li\} and Maarten IJzerman and Jayesh Desai and Solomon, \{Benjamin J.\}",

note = "Funding Information: JD has served as a consultant for Beigene, Lilly, Eisai, Amgen and Biocon; and institution has received research funding from Roche, Lilly, AstraZeneca/MedImmune, Beigene, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Bionomics. Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = aug,

day = "1",

doi = "10.1016/j.lungcan.2020.06.030",

language = "English",

volume = "146",

pages = "310--317",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Real world outcomes in KRAS G12C mutation positive non-small cell lung cancer

AU - Cui, Wanyuan

AU - Franchini, Fanny

AU - Alexander, Marliese

AU - Officer, Ann

AU - Wong, Hui Li

AU - IJzerman, Maarten

AU - Desai, Jayesh

AU - Solomon, Benjamin J.

N1 - Funding Information: JD has served as a consultant for Beigene, Lilly, Eisai, Amgen and Biocon; and institution has received research funding from Roche, Lilly, AstraZeneca/MedImmune, Beigene, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Bionomics. Publisher Copyright: © 2020

PY - 2020/8/1

Y1 - 2020/8/1

N2 - Background: KRAS mutations are found in 20–30 % of non-small cell lung cancers (NSCLC) and were traditionally considered undruggable. KRASG12C mutation confers sensitivity to KRASG12C covalent inhibitors, however its prognostic impact remains unclear. This study assesses the frequency, clinical features, prevalence of brain metastases and outcomes in KRASG12C NSCLC in a real-world setting. Methods: Patients enrolled in the prospective Thoracic Malignancies Cohort (TMC) between July 2012 to October 2019 with recurrent/metastatic non-squamous NSCLC, available KRAS results, and without EGFR/ALK/ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival (OS) was compared for KRAS wildtype (KRASWT) and KRAS mutated (KRASmut); and KRASG12C and other (KRASother) mutations. Results: Of 1386 NSCLC patients, 1040 were excluded: non-metastatic/recurrent (526); unknown KRAS status (356); ALK/EGFR/ROS1 positive (154); duplicate (4). Of 346 patients analysed, 144 (42 %) were KRASmut, of whom 65 (45 %) were KRASG12C. All patients with KRASG12C were active or ex-smokers, compared to 92 % of KRASother and 83 % of KRASWT. The prevalence of brain metastases during follow-up was similar between KRASmut and KRASWT (33 % vs 40 %, p = 0.17), and KRASG12C and KRASother (40 % vs 41 %, p = 0.74). The proportion of patients receiving one or multiple lines of systemic therapy was comparable. OS was similar between KRASmut and KRASWT (p = 0.54), and KRASG12C and KRASother (p = 0.39). Conclusion: Patients with KRASmut and KRASWT, and KRASG12C and KRASother NSCLC have comparable clinical features, treatment and survival. While not prognostic, KRASG12C may be an important predictive biomarker as promising KRASG12C covalent inhibitors continue to be developed.

AB - Background: KRAS mutations are found in 20–30 % of non-small cell lung cancers (NSCLC) and were traditionally considered undruggable. KRASG12C mutation confers sensitivity to KRASG12C covalent inhibitors, however its prognostic impact remains unclear. This study assesses the frequency, clinical features, prevalence of brain metastases and outcomes in KRASG12C NSCLC in a real-world setting. Methods: Patients enrolled in the prospective Thoracic Malignancies Cohort (TMC) between July 2012 to October 2019 with recurrent/metastatic non-squamous NSCLC, available KRAS results, and without EGFR/ALK/ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival (OS) was compared for KRAS wildtype (KRASWT) and KRAS mutated (KRASmut); and KRASG12C and other (KRASother) mutations. Results: Of 1386 NSCLC patients, 1040 were excluded: non-metastatic/recurrent (526); unknown KRAS status (356); ALK/EGFR/ROS1 positive (154); duplicate (4). Of 346 patients analysed, 144 (42 %) were KRASmut, of whom 65 (45 %) were KRASG12C. All patients with KRASG12C were active or ex-smokers, compared to 92 % of KRASother and 83 % of KRASWT. The prevalence of brain metastases during follow-up was similar between KRASmut and KRASWT (33 % vs 40 %, p = 0.17), and KRASG12C and KRASother (40 % vs 41 %, p = 0.74). The proportion of patients receiving one or multiple lines of systemic therapy was comparable. OS was similar between KRASmut and KRASWT (p = 0.54), and KRASG12C and KRASother (p = 0.39). Conclusion: Patients with KRASmut and KRASWT, and KRASG12C and KRASother NSCLC have comparable clinical features, treatment and survival. While not prognostic, KRASG12C may be an important predictive biomarker as promising KRASG12C covalent inhibitors continue to be developed.

UR - https://www.scopus.com/pages/publications/85087122054

U2 - 10.1016/j.lungcan.2020.06.030

DO - 10.1016/j.lungcan.2020.06.030

M3 - Article

C2 - 32619782

AN - SCOPUS:85087122054

SN - 0169-5002

VL - 146

SP - 310

EP - 317

JO - Lung Cancer

JF - Lung Cancer

ER -

Real world outcomes in KRAS G12C mutation positive non-small cell lung cancer

Abstract

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