Abstract 1341P
Background
NRAS activating mutations are observed in 1% of NSCLC. Clinical data regarding this rare subset of lung cancer are scarce and response to systemic treatment such as chemotherapy or immune checkpoint inhibitors (ICI) has never been described.
Methods
All consecutive patients with a NRAS mutated NSCLC, diagnosed between August 2014 and June 2020 in 14 French centers, were included. Clinical and molecular data were collected and reviewed from medical records. This non-interventional study was conducted in accordance with General Data Protection Regulation.
Results
Out of the 153 included patients, 100 (65%) were men, 109 (71%) were current or former smokers, and 97 (63%) had stage IV NSCLC at diagnosis. The median age was 62 years, and the most frequent histology was adenocarcinoma (81%). NRAS activating mutations were mostly found in codon 61 (75%), while codon 12 and 13 alterations were observed in 18% and 5% of patients, respectively. Concurrent EGFR mutation or ALK rearrangement were detected in 4 (3%) and 2 (1%) patients, respectively. PD-L1 expression level <1%/1-49% />50% were respectively found in 29%/25%/46% of patients. With a median follow up of 12.4 months, median overall survival (OS) of stage IV patients was 12.8 months 95%CI (9.8-20.5). No significant difference in OS was found according to the type of mutation (codon 61 vs. other), HR=0.79 95%CI (0.44-1.45). Among stage IV patients treated with platinum doublet (n=58), ICI (n= 45), or combination of both (n=8), objective response rate, and median progression free survival were respectively 41% and 5.1 months, 33% and 6.9 months, 75% and 8.6 months. The response rates to ICI in 1st/2ndor more line were 38%/29% respectively.
Conclusions
NRAS mutated NSCLC are characterized by a high frequency of codon 61 mutations, and a promising efficacy of immunotherapy in combination with chemotherapy. The high prevalence of codon 61 mutations should be considered for the development of future NRAS targeted therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
CHU Lille.
Funding
Has not received any funding.
Disclosure
D. Moro-Sibilot: Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: BMS; Financial Interests, Personal, Other: AstraZeneca. C. Descarpentries: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Novartis; Non-Financial Interests, Personal, Other: Roche; Non-Financial Interests, Personal, Other: Boehringer Ingelheim; Non-Financial Interests, Personal, Other: Pfizer. S. Baldacci: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Other, Support for ESMO congress participation: Pfizer. All other authors have declared no conflicts of interest.