Impact of colorectal liver metastases (CRLM) in patients with metastatic colorectal cancer (mCRC) receiving trifluridine/tipiracil (FTD/TPI) with or without bevacizumab (BEV) in the phase 3 SUNLIGHT trial.

3584 Background: Many patients with CRC develop CRLM during their disease, which are associated with poor prognosis. In the phase 3 SUNLIGHT trial, the addition of BEV to FTD/TPI significantly improved overall survival (OS) compared with FTD/TPI alone in patients with refractory mCRC, irrespective of mutational status, tumor sidedness, and other factors associated with poor prognosis. Here, we assessed the impact of baseline CRLM on efficacy outcomes among patients treated in SUNLIGHT. Methods: In this post hoc analysis, OS, progression-free survival (PFS), and disease control rate (DCR) were assessed in patients with and without CRLM. Differences in survival between FTD/TPI + BEV and FTD/TPI alone were assessed in each subgroup. The Kaplan-Meier method and log-rank test were used to compare differences in OS and PFS; DCRs were compared using Fisher's exact tests. The hazard ratios (HRs) for OS and PFS were estimated using a Cox proportional hazards model. Results: Of the 492 patients enrolled in SUNLIGHT, 382 (77.6%) had CLRM, comprising 194 randomized to FTD/TPI + BEV and 188 randomized to FTD/TPI alone. Among patients randomized to FTD/TPI + BEV (n=246), median OS (95% confidence interval [CI]) was 10.4 (8.6, 11.0) months and not estimable (NE) (11.1–NE) for patients with and without CRLM, respectively (HR: 1.88; P=0.005). For patients randomized to FTD/TPI alone (n=246), median OS (95% CI) was 6.5 (5.9, 8.0) months and 10.9 (9.0, 13.8) months for patients with and without CRLM, respectively (HR: 1.75; P=0.002). Similar trends were observed for PFS and DCR. When comparing treatment effects across arms, FTD/TPI + BEV resulted in longer OS and PFS compared with FTD/TPI alone in patients with and without CRLM. In patients with CRLM, the HRs for OS and PFS were 0.61 (95% CI: 0.48, 0.77; P<0.001) and 0.44 (95% CI: 0.35, 0.55; P<0.001), respectively. In patients without CRLM, the HRs for OS and PFS were 0.60 (95% CI: 0.35, 1.0; P=0.052) and 0.38 (95% CI: 0.24, 0.58; P<0.001), respectively. The DCR was also higher in patients treated with FTD/TPI + BEV compared with FTD/TPI alone (68.6% vs 38.3% in patients with CRLM and 73.1% vs 53.5% in patients without CRLM). Conclusions: The results of this analysis show that patients treated with the combination of FTD/TPI + BEV had numerically longer OS and PFS and a higher DCR than those treated with FTD/TPI alone, irrespective of whether or not patients had CRLM at baseline. Owing to the imbalance in numbers of patients with and without CRLM, the data need to be interpreted with caution. Clinical trial information: NCT04737187 .