590P - A retrospective study of the prevalence and clinical outcomes of KRAS G12C mutated advanced non-small cell lung cancer (NSCLC) in Australian patients (pts)

Background

KRAS mutations are the most common molecular alteration in NSCLC, with the KRAS ^G12C variant reported in 12-13% of Western patients. We sought to determine the prevalence and characteristics of Australian pts with advanced NSCLC harbouring the KRAS ^G12C mutation.

Methods

We performed a multi-centre, retrospective review of pts diagnosed with advanced NSCLC in 2018 - 2019 for whom a KRAS result was available. Comprehensive clinicopathological and outcome data was collected and analysed for all KRAS ^G12C patients, and subsets of pts with non-G12C mutations (KRAS ^other) and KRAS wild type (KRAS ^WT).

Results

1085 pts from 17 sites were included, of whom 189 (17.4%) were KRAS ^G12C. Comprehensive data was collected on 163 KRAS ^G12C, 116 KRAS ^other and 104 KRAS ^WT pts. Baseline characteristics are summarised in the table. The 3 cohorts were similar in terms of age, sex, ECOG and metastatic disease at diagnosis. The KRAS ^G12C cohort had fewer never smokers (p <0.0001) and a trend to more PDL1 ≥50% patients (p=0.10) than the KRAS ^WT cohort. Comparable proportions in each cohort received any systemic therapy or any immunotherapy for advanced disease, with a similar number of lines of therapy delivered. Only 3 KRAS ^G12C patients received targeted therapy because of limited access. Median overall survival (mOS) in the KRAS ^G12Ccohort was 11.9 months (mo), compared to 17.0 mo in the KRAS ^other cohort (p=0.34), 26.8 mo in the KRAS ^WTcohort (p=0.02) and 17.6 mo in the KRAS ^WT cohort with EGFR/ALK/ROS1 mutated patients excluded (p=0.17). Table: 590P

Conclusions

Our study demonstrated a prevalence of KRAS ^G12C mutations of 17.4% among Australian pts with advanced NSCLC. The KRAS ^G12C, KRAS ^other and KRAS ^WT cohorts had similar patient and treatment patterns, although smoking history was more common in pts with a KRAS mutation. In the absence of other key driver mutations, there was no significant difference in mOS between cohorts.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Walter and Eliza Hall Institute of Medical Research.

Funding

Amgen.

Disclosure

B. Markman: Financial Interests, Personal, Advisory Board: Amgen, Merck, Bristol Myers Squibb, BeiGene, AstraZeneca; Financial Interests, Institutional, Research Funding: Amgen. B. Solomon: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Merck, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Roche/Genentech; Financial Interests, Personal, Advisory Board: Amgen, Roche-Genentech, Eli Lilly, Takeda, Janssen; Financial Interests, Personal, Full or part-time Employment, Employed as a consultant Medical Oncologist at Peter MacCallum Cancer Centre: Peter MacCallum Cancer Centre; Financial Interests, Personal, Member of Board of Directors: Cancer Council of Victoria, Thoracic Oncology Group of Australasia; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Steering Committee Member, Principal Investigator and Steering committee Chair: Roche/Genentech, Pfizer; Financial Interests, Institutional, Steering Committee Member: Novartis. L.M. Nott: Financial Interests, Institutional, Research Funding: Roche, Servier; Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Merck, Roche, Pfizer, MSD, Servier, Ipsen, AstraZeneca, Novartis; Financial Interests, Personal, Other, Honorarium: MSD, Amgen, Roche, Bristol Myers Squibb, Celgene. R. Roberts-Thomson: Financial Interests, Personal, Advisory Board: Bristol Myer Squibbb, Merck Sharpe and Dohme, Pfizer, AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myer Squibbb, Merck Sharpe and Dohme, Novartis, AstraZeneca, Pierre Fabre. B. Hughes: Financial Interests, Personal, Advisory Board: MSD, BMS, Pfizer, Roche, AstraZeneca, Takeda, Sanofi, Esai, Amgen; Financial Interests, Institutional, Research Funding: Amgen. N. Pavlakis: Financial Interests, Personal, Advisory Board: MSD, Merck, BMS, AstraZeneca, Takeda, Pfizer, Roche, Amgen, BeiGene; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Pfizer, Roche, Takeda, Pierre-Faber, Illumina, Bayer; Financial Interests, Institutional, Research Funding: Bayer, Pfizer, Roche. S. Parakh: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, Roche, AstraZeneca; Financial Interests, Institutional, Research Funding: Bayer, Roche. D. Brungs: Financial Interests, Personal, Speaker, Consultant, Advisor: MSD. S.E. Bowyer: Financial Interests, Personal, Advisory Board: Lilly, Ipsen, Sanofi, MSD, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, MSD, Sanofi. L. Warburton: Financial Interests, Personal, Advisory Board: Roche, Novartis, MSD, AstraZeneca, Bristol Myers Squibb. S.J. Harris: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb. S. Ramanujam: Financial Interests, Personal, Full or part-time Employment, Until April 2023: Amgen. A. Wang: Financial Interests, Personal, Full or part-time Employment: Amgen. All other authors have declared no conflicts of interest.