1401P - Impact of KRAS mutation on non-small cell lung cancer survival outcomes

Background

The Kristen Rat Sarcoma (KRAS) activating mutation represents the most frequent oncogenic alteration in non-squamous non-small cell lung cancer (nsq-NSCLC). We aimed to describe the characteristics, treatment patterns and survival outcomes of a real-world population of advanced NSCLC according to the KRAS status.

Methods

From January 2011 to December 2021, we identified from the ESME database (NCT03848052) patients with a metastatic nsq-NSCLC. Patients with other druggable oncogenic alterations were excluded. Patients were grouped according to KRAS status: mutated (KRASm) versus wild-type (KRASwt). We analyzed KRASm subtype prevalence, patient and tumor characteristics, treatment history, and overall survival (OS). We analyzed patients’ survival outcomes according to the period of care to assess the impact of the implementation of immunotherapy as standard of care in France (available from 2017 in monotherapy and 2019 in combination with chemotherapy). Given that the proportional-hazards assumption is not verified, we used the restricted mean survival time (RMST). RMST is the average survival time until a milestone time point.

Results

We identified 6 818 patients of whom 2 916 (42.8%) were KRASm. Among the KRASm tumors, 1272 (43.6%) were KRAS-G12C. According to KRAS-status (mutant vs. wild-type): 41.4% vs. 33.8% were women (p<0.01); 3.9% vs. 10.9% were non-smokers (p<0.01); 45.0% vs. 37.0% had a high PD-L1 expression (>50%; p<0.01), 33.5% vs. 30.8% had brain metastasis (p=0.06). After a median follow-up of 52.9 months (95% CI 51.2 - 55.5), median OS was 13.2 months (95% CI 12.3 - 14.1) for KRASm and 15.1 months (95% CI 14.4 - 15.5) for KRASwt patients (p<0.01).

Table: 1401P

RSMT for OS at one year according to KRAS status and period of care

Conclusions

KRASm appears to be a poor prognostic factor for metastatic nsq-NSCLC. The advent of chemotherapy-immunotherapy seems to have mitigated this pejorative impact. The prevalence of high PD-L1 in the KRASm tumors may explain this improvement of survival outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Unicancer.

Funding

This work was supported by Unicancer. Industrial partners (AstraZeneca, Roche, Janssen, MSD, BMS, Amgen) financially support the ESME Lung Cancer database but Unicancer manages the database (i.e. data collection, analysis and publication) independently.

Disclosure

Q. Thomas: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Other: AstraZeneca. T. Filleron: Financial Interests, Personal, Other, working group: Janssen-Cilag; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Other, working group: Roche; Other, Consulting (compensated to my institution): Cellectis. J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, Msd, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, Takeda, Sanofi; Financial Interests, Personal, Expert Testimony: Ose Immunotherapeutics; Financial Interests, Institutional, Invited Speaker: Merck Portugal; Non-Financial Interests, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca; Non-Financial Interests, Member, Secretary of the Lung Cancer Group at the EORTC: EORTC. 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, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Takeda, Boehringer Ingelheim; Financial Interests, Personal, Other, DMSB: Roche. 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. 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, Pfizer; Financial Interests, Institutional, Funding: Roche, AstraZeneca, Janssen, MSD, Pfizer, BMS, Lilly, Boehringer Ingelheim, GSK, Chugaï, Chiesi, Novartis, Takeda, Bayer, SanofiAventis. C. Audigier Valette: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, AstraZeneca, Sanofi, Janssen; Financial Interests, Personal, Invited Speaker: Pfizer. C. Chouaid: Financial Interests, Personal, Advisory Board: AZ, BI, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Janssen and Amgen; Financial Interests, Institutional, Funding: AZ, BI, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Janssen and Amgen. S. Hiret: Financial Interests, Institutional, Advisory Board: BMS, Takeda, AstraZeneca, Sanofi, Roche; Financial Interests, Institutional, Other, support for attending meeting: Novartis. A.T. Stancu: Financial Interests, Institutional, Invited Speaker: Sanofi, AstraZeneca, Amgen, MSD, AstraZeneca, BMS; Financial Interests, Personal, Expert Testimony: BMS, Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Invited Speaker: IFCT. L. Bosquet: Financial Interests, Institutional, Full or part-time Employment, In charge of scientific projects at Unicancer, Health Data and Partnership Department: Unicancer. All other authors have declared no conflicts of interest.