614P Effect of KRASG12 mutations on overall survival in patients with refractory metastatic colorectal cancer: A post-hoc analysis of the phase III SUNLIGHT trial

SUNLIGHT, a randomized phase 3 study comparing trifluridine/tipiracil (FTD/TPI) + bevacizumab (FTD/TPI + bev) vs FTD/TPI monotherapy in patients (pts) with metastatic colorectal cancer (mCRC), demonstrated a 3.3-month increase in overall survival (OS) from 7.5 months with FTD/TPI monotherapy to 10.8 months with FTD/TPI + bev (HR, 0.61; 95% CI, 0.49 – 0.77; P<0.001). Here reported are data on the effects of KRASG12 mutational status on OS. A post-hoc analysis of the SUNLIGHT trial was conducted in pts with a KRASG12 mutation to assess the effect of the mutation on OS in the overall population treated with FTD/TPI monotherapy and FTD/TPI + bev. In addition, a subgroup analysis according to the KRASG12 mutational status was conducted to assess the treatment benefit associated with FTD/TPI + bev vs FTD/TPI monotherapy on OS. In the overall population, a similar OS trend was observed regardless of KRASG12 mutational status. In pts with a KRASG12 mutation, mOS was 8.34 months (95% CI: 7.49 – 9.59); whereas, in pts with no KRASG12 mutation, mOS was 9.17 months (95% CI: 8.15 – 10.94). A non-detrimental effect on OS was observed in pts with a KRASG12 mutation vs in pts with no KRASG12 mutation (HR, 1.09; 95% CI: 0.87 – 1.36) in the overall population treated with both FTD/TPI monotherapy and FTD/TPI + bev. Similar results were observed when the analysis was restricted to the RAS mutant subgroup. In the subgroup analysis, pts treated with FTD/TPI + bev were more likely to benefit with a higher OS than those treated with FTD/TPI monotherapy in each subgroup (KRASG12 mutated or not). In the KRASG12 mutant subgroup, mOS was 9.36 months (95% CI: 8.15 – 10.94) with FTD/TPI + bev vs 7.23 months (95% CI: 6.31 – 9.13) with FTD/TPI monotherapy (HR, 0.67; 95% CI: 0.48 – 0.93). In the subgroup with no KRASG12 mutation, mOS was 11.27 months (95% CI: 9.56 – 14.19) with FTD/TPI + bev vs 7.13 months (95% CI: 5.88 – 8.87) with FTD/TPI monotherapy (HR, 0.59; 95% CI: 0.43 – 0.81). The presence of a KRASG12 mutation had no detrimental effect on OS, with a similar OS trend regardless of whether the pts had a KRASG12 mutation or not. The benefit of FTD/TPI + bev vs FTD/TPI on OS was confirmed independently of the KRASG12 mutational status.