Results from SUNLIGHT study point to practice-changing care for patients with refractory metastastic colorectal cancer

SUNLIGHT study, an open-label controlled two-arm, phase III comparison study was designed to validate the efficacy and safety of the orally administered combination of trifluridine/tipiracil plus monoclonal antibody bevacizumab versus trifluridine/tipiracil alone in the third-line treatment of patients with refractory metastatic colorectal cancer (mCRC) who had progressed after two lines of prior therapy.

Around 50% of colorectal cancer patients will ultimately develop metastasis, with a five- year survival rate of only 11%. The prognosis for patients with refractory disease remains poor, with median survival generally between 4-8 months. With limited treatment options available, the standard of care for this patient population currently includes trifluridine/tipiracil or regorafenib as monotherapy, or in combination with other approved agents for some patients.

“There is an urgent, unmet clinical need to identify new and more effective treatment strategies to improve the survival and quality of life of our patients. Representing an important step in this direction, the SUNLIGHT phase III study was designed to evaluate the true clinical value of combining trifluridine/tipiracil with bevacizumab,” says Josep Tabernero, first author of this study published today in the New England Journal of Medicine, and Head of the Medical Oncology Service of the Vall d’Hebron University Hospital (HUVH), Campus Hospital Vall d’Hebron Barcelona.

SUNLIGHT enrolled 492 patients across 103 study locations who had received a maximum of two prior chemotherapy regimens for the treatment of advanced colorectal cancer and had demonstrated progressive disease or intolerance to their last regimen. These patients were randomized (1:1) to receive trifluridine/tipiracil in combination with bevacizumab, or trifluridine/tipiracil monotherapy.

The primary endpoint of this phase III clinical trial was overall survival, and secondary outcome measures were overall response rate, disease control rate, treatment-emergent adverse events, and quality of life.

Potentially practice-changing data

The SUNLIGHT study investigators, including Elena Élez, Head of VHIO’s Colorectal Cancer Group, reported an improved median survival of 3.3 months with trifluridine/tipiracil plus bevacizumab, from 7.5 months with trifluridine/tipiracil monotherapy to 10.8 months with the combination regimen.

“An improved survival rate of over three months in metastatic colorectal cancer is considered as statistically as well as clinically relevant. These present data could therefore promise a new standard of care for patients with refractory disease who have progressed after two prior lines of therapy,” observes Tabernero.

Progression-free survival was 2.4 months with trifluridine/tipiracil alone versus 5.6 months combined with bevacizumab. Time to deterioration in global health status was 4.7 months and 8.5 months, respectively. Quality of life was graded according to the ECOG Performance Status Scale. Median time to worsening to a grade 2 or more was 9.3 months with the combination compared with 6.3 months in those patients receiving trifluridine/tipiracil alone.

“In addition to the magnitude of benefit observed in patients who received the combination, adding bevacizumab to trifluridine/tipiracil did not increase the risk of serious adverse or adverse events. Improved survival was observed across all subgroups independently of tumor sidedness, RAS mutational status, and receipt of prior bevacizumab, indicating that the combination regimen is an option for all clinically relevant subgroups,” adds Elena Élez, a Senior Consultant of HUVH’s Medical Oncology Department.

SUNLIGHT is the first phase III study to validate a new third-line treatment strategy by showing improved efficacy over an existing active regimen in these patients, with a greater benefit than that observed in other trials, and in a population that included patients with poor prognostic factors such as RAS mutations.

“Our data point to trifluridine/tipiracil plus bevacizumab as a new standard of care. This combination therapy could therefore open a much needed, more effective treatment avenue for patients with refractory metastatic colorectal cancer who have progressed after two lines of therapy,” concludes Josep Tabernero.

Josep Tabernero will present updated results of this new pharmacological combination for patients with advanced refractory colorectal cancer at the annual ASCO congress, which will be held in Chicago from June 3 to 6 and which brings together the greatest international experts in cancer to present the most outstanding advances in clinical oncology.

Reference

Gerald W. Prager, M.D., Julien Taieb, M.D., Ph.D., Marwan Fakih, M.D., Fortunato Ciardiello, M.D., Ph.D., Eric Van Cutsem, M.D., Ph.D., Elena Elez, M.D., Ph.D., Felipe Melo{q2} Cruz, M.D., Ph.D., Lucjan Wyrwicz, M.D., Ph.D., Daniil Stroyakovskiy, M.D., Ph.D., Zsuzsanna Pápai, M.D., Pierre-Guillaume Poureau, M.D., Gabor Liposits, M.D., Chiara Cremolini, M.D., Ph.D., Igor Bondarenko, M.D., Ph.D., Dominik Paul Modest, M.D., Karim A. Benhadji, M.D.,Nadia Amellal, M.D., Catherine Leger, M.Sc., Loïck Vidot, M.Sc., and Josep Tabernero, M.D., Ph.D., for the SUNLIGHT Investigators. Trifluridine–Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. New England Journal of Medicine. DOI: NEJMdo007030