86P - KRAS G12 versus G13 codon mutation survival rates for different lines of MCRC treatment: Real-world data over a 4 year period

Background

KRAS is an oncogene associated with poor prognosis in colorectal cancers. Trifluridine/Tipiracil (TT) is often used in the 3^rd-line setting for pts with MCRC irrespective of KRAS mutation status. Since 2022, three retrospective publications have shown differing results in terms of outcome to TT based on KRAS status. One showed pts with a G12 mutation did not have a survival advantage with TT compared to placebo whereas those with a G13 mutation did (Van der Haar 2023). However, two other publications showed a survival benefit, with TT based therapy regardless of KRAS codon 12 or 13 mutation status (Yoshino 2022, Tabenero ESMOabs 2023).

Methods

We retrospectively analysed survival data for different lines of chemotherapy for pts with KRAS G12 and G13 mutations over 4 years (2018-2021). Prism was used to analyse data using both Gehan-Breslow-Wilcoxson test and Logrank test.

Results

306 patients were evaluated, of which 80% (n= 246) were KRAS G12 mutated. The OS for the whole group was 25 mths with no significant difference between G12 and G13 patients (760/757 days, p = 0.99). OS for first-line treatment (277 pts) was 19.2 mths and 18 mths (p = 0.43). 1^st-line Oxaliplatin based chemotherapy (148 pts) was 19 v 23.4 mths (p = 0.94). 56% (174 pts) who received second line treatment had an OS of 12.5 and 13 mths (P = 0.77). 2nd-line Irinotecan (90 pts) was 11.8 v 13.5 mths (p = 0.79). The OS for the 21% (n= 66) (G13: 13 pts) who received TT as third line was 6.9 v 8.2 mths (p = 0.42). OS for G12D (42%) v G12C (8%) v other G12 mutations (50%) was 23.3 v 32.8 v 25.5 mths (p=0.39).

Conclusions

Based on more than 300 pts collected from a 4-year period, neither G12 or G13 KRAS mutations influenced the survival for pts receiving 1^st, 2^nd or 3^rd line therapies. However, these results have to be considered with some caution due to the rarity of the G13 mutation (20% of cohort – 60 pts).

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.