SUNLIGHT: What the Colorectal Cancer Trial Found

Late-line colorectal cancer, and what is left to try

By the time metastatic colorectal cancer has been through the standard drugs, the shelf is nearly bare. Fluoropyrimidine chemotherapy, oxaliplatin, irinotecan, an anti-VEGF antibody, and for RAS wild-type tumors an anti-EGFR antibody: that is the sequence, and it runs out.

Trifluridine and tipiracil, sold as Lonsurf, is one option after that point. It is a tablet, not an infusion, which matters after years attached to a drip.

SUNLIGHT asked whether adding an older drug back on top would help.

What the tablet does

Lonsurf combines two compounds in a fixed ratio. Trifluridine is a thymidine-based nucleoside analog. It looks enough like a DNA building block that cells stitch it into their DNA, where it jams DNA synthesis and stops the cell dividing.

The problem is that the body destroys trifluridine fast, using an enzyme called thymidine phosphorylase. That is what tipiracil is for. Tipiracil blocks the enzyme, so more trifluridine survives to reach the tumor.

Bevacizumab works on a different target. It binds VEGF, a signal tumors use to grow new blood vessels, and stops VEGF reaching its receptors on the cells lining those vessels. Fewer new vessels means a tumor with a poorer supply line.

The trial

SUNLIGHT randomly assigned 492 adults, 246 to each group. All had advanced colorectal cancer and no more than two previous chemotherapy regimens.

One group took trifluridine-tipiracil alone. The other took the same tablet plus bevacizumab. The primary endpoint was overall survival.

Secondary endpoints included progression-free survival and safety. One more mattered a great deal.

What the trial found

Median overall survival was 10.8 months with the combination and 7.5 months with the tablet alone. The hazard ratio for death was 0.61, with a 95 percent confidence interval of 0.49 to 0.77, and a p-value below 0.001.

A hazard ratio compares how fast deaths accumulate in one group against the other. At 0.61 the rate ran about 39 percent lower with bevacizumab added. The confidence interval is the range the true value most likely occupies, and it stayed well below 1.

Median progression-free survival was 5.6 months versus 2.4 months, hazard ratio 0.44, again with a p-value below 0.001. Progression-free survival is the time before scans show the cancer growing.

The endpoint about daily life

The third result is the one worth sitting with.

The trial tracked how long it took for a person's ECOG performance-status score to slip from 0 or 1 to 2 or more. That scale runs 0 to 5. Zero means fully active. Two means up and about more than half the waking day, but unable to work.

That median was 9.3 months with the combination and 6.3 months without, hazard ratio 0.54.

Three extra months of independence is a different number from three extra months of survival. For many people it is the one that decides things.

The cost, in blood counts

The most common adverse events in both groups were neutropenia, nausea and anemia. No deaths were attributed to treatment.

The US label puts the combination's toll more precisely. Among the 246 patients who took Lonsurf with bevacizumab, severe or life-threatening myelosuppression included neutropenia in 52 percent and anemia in 5 percent. Myelosuppression means the bone marrow makes fewer blood cells. Neutropenia is a shortage of neutrophils, the white cells that fight bacteria.

Twenty-nine percent needed granulocyte colony-stimulating factor, a drug that pushes the marrow to make more white cells.

The label instructs teams to check complete blood counts before each cycle and again on day 15. It also sets numeric floors: a cycle does not start unless the absolute neutrophil count is at least 1,500 per cubic millimeter and platelets at least 75,000. Our page on chemotherapy explains what those counts govern.

The dose is 35 milligrams per square meter twice daily with food, on days 1 to 5 and days 8 to 12 of a 28-day cycle.

When to get checked

Two different moments matter here, and they need different answers.

For anyone on this treatment, the urgent signs are infection signs: fever, chills, sore throat, or feeling suddenly unwell. With neutropenia at 52 percent, a fever is not something to sleep on.

For everyone else, the question is bowel cancer itself. NCI lists blood in the stool, whether bright red or very dark, a change in bowel habits, diarrhea or constipation, a feeling the bowel has not emptied, narrower stools, abdominal discomfort, unexplained weight loss, fatigue and vomiting.

Screening carries the clearest thresholds. The US Preventive Services Task Force gives colorectal screening a grade A for adults aged 50 to 75, and a grade B for adults aged 45 to 49. Our page on colorectal cancer screening sets out the test options.

The numbers behind the setting

For 2026, American Cancer Society projections carried by SEER give 158,850 new US colorectal cancer cases and 55,230 deaths. Five-year relative survival for cases from 2016 to 2022 is 65.4 percent overall.

Split by spread, that is 91.3 percent for localized disease, 75.2 percent with regional lymph nodes involved, and 16.9 percent once the cancer has spread to distant organs. Twenty-three percent of US cases are already distant at diagnosis.

SUNLIGHT sits inside that last group, and inside the part of it that has already used two lines of treatment. Registry averages cover everyone, so they are a poor guide here and no guide at all to one person.

What this trial cannot tell you

It was open-label. Everyone knew who was getting the infusion, and performance status is judged partly by opinion.

The comparison was the tablet alone. That is a fair test of what bevacizumab adds. It does not rank the combination against every other option at this stage.

Participants had at most two previous regimens. Earlier trials here enrolled people who had been through more, so the numbers do not line up across trials.

And a median is a middle, not a promise. Half the combination group lived less than 10.8 months.

Sources

• Prager GW and others, Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer, New England Journal of Medicine 2023 (record and abstract via NCBI) — https://pubmed.ncbi.nlm.nih.gov/37133585/
• FDA prescribing information for LONSURF, via the openFDA drug label API — https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22LONSURF%22&limit=1
• FDA prescribing information for AVASTIN, via the openFDA drug label API — https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22AVASTIN%22&limit=1
• NCI PDQ, Colon Cancer Treatment (Patient Version) — https://www.cancer.gov/types/colorectal/patient/colon-treatment-pdq
• US Preventive Services Task Force, Colorectal Cancer: Screening — https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/colorectal-cancer-screening
• SEER Cancer Stat Facts, Colorectal Cancer — https://seer.cancer.gov/statfacts/html/colorect.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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