Trifluridine/tipiracil plus bevacizumab prolongs survival in refractory colorectal cancer
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The addition of bevacizumab to trifluridine/tipiracil demonstrated a statistically significant and clinically meaningful improvement in OS vs. trifluridine/tipiracil alone among adults with refractory metastatic colorectal cancer.
The finding, presented at ASCO Gastrointestinal Cancers Symposium, represents a 39% reduction in the risk for death among this patient population.
Rationale and methods
“The prognosis for [patients with] metastatic colorectal cancer who do not respond to chemotherapy remains poor, with median survival times typically ranging from 4 to 8 months,” Josep Tabernero, MD, PhD, head of medical oncology at Vall d’Hebron University Hospital in Barcelona, Spain, and principal investigator for the SUNLIGHT trial, said in a press release. “Coupled with the fact that cases of colorectal cancer are increasing, there is an urgent need for new treatment options that can extend survival in patients with metastatic colorectal cancer in the later stages of disease.”
The global phase 3 SUNLIGHT trial evaluated the efficacy and safety of trifluridine/tipiracil (Lonsurf; Taiho Oncology, Servier) both with and without bevacizumab (Avastin, Genentech) in patients with refractory metastatic colorectal cancer following disease progression on or intolerance to two chemotherapy regimens.
Researchers randomly assigned 492 patients in a 1:1 ratio to receive either trifluridine/tipiracil monotherapy (35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle) or combined with bevacizumab (5 mg/kg on days 1 and 15).
OS served as the primary endpoint. Secondary endpoints included PFS, overall response rate, disease control rate, quality of life and safety.
Findings
Results showed a statistically significant 3.3-month improvement in median OS with the investigational combination compared with trifluridine/tipiracil monotherapy (10.8 months vs. 7.5 months, HR = 0.61, 95% CI, 0.49-0.77).
Researchers also observed a higher 12-month OS rate with the addition of bevacizumab to trifluridine/tipiracil (43% vs. 30%), as well as longer median PFS (5.6 months vs. 2.4 months; HR = 0.44; 95% CI, 0.36-0.54).
“The survival benefit was observed across all subgroups, irrespective of age, sex, location of primary disease, number of metastatic sites and RAS mutation status, indicating that trifluridine/tipiracil plus bevacizumab may be a good option for all clinically relevant subgroups,” Tabernero told Healio.
Grade 3 or higher treatment-associated adverse events occurred at similar rates in the bevacizumab and trifluridine/tipiracil monotherapy groups (72.4% vs. 69.5%). The most frequent severe treatment-emergent adverse events for both groups included neutropenia (43.1% in the combination arm vs. 32.1% in the trifluridine/tipiracil arm) and anemia (6.1% vs. 11%).
Researchers noted no new safety signals.
“On top of the magnitude of benefit, adding bevacizumab to trifluridine/tipiracil did not increase the risk for serious adverse events or adverse events leading to discontinuation,” Tabernero told Healio. “Although the combination of trifluridine/tipiracil plus bevacizumab was associated with higher rates of severe neutropenia, there was no increase in the incidence of febrile neutropenia. Taking in consideration all this data, the combination of trifluridine/tipiracil plus bevacizumab represents a new standard of care for the treatment of patients with refractory metastatic colorectal cancer who have progressed after two lines of therapy.”
Implications
The study sponsors plan to submit the data to the regulatory authorities with a goal to bring the trifluridine/tipiracil-bevacizumab combination to patients as early as possible, Tabernero told Healio.
“Moreover, expanded analysis on the objectives of the study, as well as subgroup analysis, will be presented in upcoming meetings and journal publications,” he said.
“Hopefully, the efficacy and safety data of the combination of trifluridine/tipiracil and bevacizumab will be evaluated by the oncologic professional societies to eventually include this combination therapy in the metastatic colorectal cancer guidelines, on top of the existing recommendations,” Tabernero added.
References:
- Servier and Taiho Oncology present overall survival data for trifluridine/tipiracil (Lonsurf) in combination with bevacizumab in patients with refractory metastatic colorectal cancer at 2023 ASCO Gastrointestinal Cancers Symposium (press release). Available at www.taihooncology.com/us/news/2023-01-17_sunlight_asco_gi/. Published Jan. 17, 2023. Accessed Jan. 23, 2023.
- Tabernero J, et al. Abstract 4. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 19-21, 2023; San Francisco.
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Tabernero J, et al. Abstract 4. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 19-21, 2023; San Francisco.
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