1407P - Characteristics and treatment sequences of patients (pts) with KRAS G12C, other KRAS and non-KRAS advanced or metastatic (AM) non-small cell lung cancer (NSCLC) in the French ESME cohort

Background

KRAS G12C mutation is found in 14% of NSCLC. Pts with KRAS G12C AM NSCLC have not been well characterized in routine clinical setting. Our objective was to describe pts with KRAS G12C AM NSCLC and compare them to pts with other KRAS and non-KRAS AM NSCLC.

Methods

We performed a retrospective observational cohort study of AM NSCLC pts included in the Epidemio-Strategy and Medical Economics (ESME) Lung Cancer Database and diagnosed between 2015 and 2021. Pts tested for KRAS mutation before first-line treatment (L1 or during the disease for pts who didn’t receive any L1) were divided in 3 subgroups: KRAS G12C (positive KRAS G12C mutation), other KRAS (positive for KRAS mutation other than G12C) and non-KRAS (negative for all KRAS mutations).

Results

A total of 1073 pts carried KRAS G12C (15%), 1642 other KRAS (23%) and 4295 non-KRAS (61%). Among KRAS G12C pts, 58% were male, and the median age was 63 years. The majority (98%) had a smoking history. 68% had an ECOG PS of 0-1. 69% had de novo stage IV. The most frequent metastatic sites involved were bone (42%), brain (35%) and contralateral lung (27%). STK11 appears to be the most common co-mutation (54%) when tested. When PD-L1 status was screened (43%), one third had PD-L1≥50%, and one third had PD-L1<1%. In 2015, most pts received platinum-based chemotherapy (CT) alone (89%) in 1L; this proportion decreased to 55% in 2019 given the benefit of immunotherapy (IO) combined to CT or as monotherapy. In L2, treatments were evenly used in 2015 but IO monotherapy peaked in 2018 to 65%. In L3, IO and other treatments were quite stable over time. The patient and disease characteristics were similar in other KRAS and non-KRAS pts, except a higher proportion of non-smokers (20%) and a less frequent STK11 mutation (28%) in non-KRAS pts than in the 2 other groups. Treatments were similar in the 3 subgroups except the peak of IO observed in L2 in 2017 and in L3 in 2018 for other KRAS pts.

Conclusions

In real-world clinical practice, clinical characteristics and treatment sequences of pts with KRAS G12C AM NSCLC are similar to those of other KRAS mutations or wild-type KRAS pts except for the prevalence of STK11 co-mutation and the proportion of non-smokers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Unicancer.

Funding

The ESME Lung Cancer Database receives financial support from industrial partners (AstraZeneca, Merck Sharp and Dohme, Bristol Myers Squibb, Roche, Janssen, Amgen) but Unicancer manages the database (data collection, analysis and publication) independently. This study was funded by Amgen Ltd.

Disclosure

N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Non-Financial Interests, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Family member is an employee: AstraZeneca. M. Pérol: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Eisai, Ipsen; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, BMS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Medscape; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Takeda, Boehringer Ingelheim; Financial Interests, Personal, Steering Committee Member: Roche; Financial Interests, Personal, Other, DMSB: Roche. D. Debieuvre: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Janssen, Pfizer, Ose Immunotherapeutics, Novartis, SanofiAventis, Amgen, Roche, Ipsen; Financial Interests, Personal, Invited Speaker: Gilead, Takeda; Financial Interests, Personal, Coordinating PI: Pfizer; Financial Interests, Institutional, Funding: Roche, AstraZeneca, Janssen, MSD, Pfizer, BMS, Lilly, Boehringer Ingelheim, GSK, Chugaï, Chiesi, Novartis, Takeda, Bayer, SanofiAventis. L. Bosquet: Financial Interests, Institutional, Full or part-time Employment, In charge of scientific projects at Unicancer, Health Data and Partnership Department: Unicancer. C. Veillard: Financial Interests, Personal, Full or part-time Employment, Medical Advisor Amgen France: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. M. Caillon, L. Tzala, G. Desamericq: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. C. Audigier Valette: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, AstraZeneca, Sanofi, Janssen; Financial Interests, Personal, Invited Speaker: Pfizer.