Adding bevacizumab to treatment with trifluridine-tipiracil improves outcomes in patients with refractory, metastatic colorectal cancer (CRC), according to research published in The New England Journal of Medicine.

Researchers found that adding bevacizumab to trifluridine-tipiracil significantly improved overall survival (OS) and progression-free survival (PFS) in the phase 3 SUNLIGHT trial ( Identifier: NCT04737187).

The trial included 492 patients with advanced CRC who had received no more than 2 previous chemotherapy regimens. They were randomly assigned to trifluridine-tipiracil plus bevacizumab (n=246) or trifluridine-tipiracil alone (n=246). Baseline characteristics were balanced between the arms. 

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All patients had received previous fluoropyrimidine-based therapy, 72.0% had received previous anti-VEGF therapy, and 93.7% of patients with RAS wild-type disease had received previous anti-EGFR therapy. Patients had received bevacizumab as part of their first treatment regimen (47.8%), their second regimen (43.9%), or both (20.3%).

The median duration of study treatment was 5.0 months in the bevacizumab arm and 2.1 months in the trifluridine-tipiracil-alone arm. The median follow-up was 14.2 months and 13.6 months, respectively.

The median OS was 10.8 months in the bevacizumab arm and 7.5 months in the trifluridine-tipiracil-alone arm (hazard ratio [HR], 0.61; 95% CI, 0.49-0.77; P <.001). The 12-month OS rate was 43% and 30%, respectively. 

The median PFS was 5.6 months in the bevacizumab arm and 2.4 months in the trifluridine-tipiracil-alone arm (HR, 0.44; 95% CI, 0.36-0.54; P <.001). The 12-month PFS rate was 16% and 1%, respectively.

The researchers noted that the survival benefits of bevacizumab were observed regardless of patient age, sex, location of primary disease, number of metastatic sites, RAS mutation status, and prior treatment with bevacizumab.

Nearly all patients (98.0%) had an adverse event (AE). Grade 3 or higher AEs occurred in 72.4% of patients in the bevacizumab arm and 69.5% of those in the trifluridine-tipiracil-alone arm. Serious AEs occurred in 24.8% and 31.3%, respectively. 

The most common AEs in both treatment arms were neutropenia, nausea, and anemia. AEs that were more common in the bevacizumab arm than in trifluridine-tipiracil-alone arm were hypertension (10.2% vs 2.0%), nausea (37.0% vs 27.2%), and neutropenia (62.2% vs 51.2%). 

Discontinuation of study treatment due to AEs occurred in 12.6% of patients in both arms. There were no treatment-related deaths. 

“The data from this trial confirm that FTD-TPI [trifluridine-tipiracil] plus bevacizumab is an effective treatment option for patients with refractory metastatic colorectal cancer, irrespective of mutational status, which side the tumor is on, and whether patients have previously been treated with bevacizumab,” the researchers concluded.

Disclosures: This research was supported by Servier and Taiho Oncology. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Prager GW, Taieb J, Fakih M, et al. Trifluridine–tipiracil and bevacizumab in refractory metastatic colorectal cancer. N Engl J Med. Published online May 4, 2023. doi:10.1056/NEJMoa2214963