Observational Study Regarding the Combination of Fluoropyrimidine and Bevacizumab in Patients With mCRC

Multicenter Observational Study Regarding the Combination of Fluoropyrimidine and Bevacizumab in the Treatment of Patients With Metastatic Colorectal Cancer

This study will enroll patients with metastatic colorectal cancer treated with the combination of Trifluridine/Tipiracile and Bevacizumab across 15 italian centers.

The FLOWER study is a multicenter, observational investigation evaluating the real-world effectiveness and safety of a therapeutic combination of fluoropyrimidines and bevacizumab in patients with metastatic colorectal cancer (mCRC).

Colorectal cancer remains one of the most common and lethal cancers in Italy, and although early screening has improved detection rates, a substantial proportion of patients still present with or eventually develop metastatic disease. For those whose tumors do not exhibit specific molecular characteristics (such as dMMR or MSI-high), standard first- and second-line treatments often involve chemotherapy regimens based on fluoropyrimidines combined with agents like oxaliplatin or irinotecan, alongside targeted therapies such as bevacizumab or, in RAS wild-type tumors, anti-EGFR drugs.

However, once patients become refractory to these initial therapies, treatment options become more limited. While some benefit from newer targeted approaches like the combination of cetuximab and encorafenib in BRAF-mutated cancers, many patients without actionable mutations rely on drugs like regorafenib or trifluridine-tipiracil, which have shown only modest benefits. Recent evidence from the SUNLIGHT trial has shown that adding bevacizumab to TAS-102 significantly improves survival in this setting, highlighting the potential benefit of combining antiangiogenic agents with chemotherapy even in heavily pretreated patients. Building on this rationale, the FLOWER study aims to assess how effective and safe the combination of fluoropyrimidines and bevacizumab is when used in daily clinical practice.

The primary objective of the study is to evaluate overall survival, while secondary endpoints include progression-free survival, response rates, safety, and identification of clinical or molecular factors that may predict outcomes. The study will include approximately 300 patients treated between 2023 and 2026. Both retrospective and prospective data will be collected, and no additional procedures, exams, or financial costs are imposed on the healthcare system. The study follows ethical guidelines laid out by the Declaration of Helsinki and has been approved by the regional ethics committee.

Inclusion Criteria:

• Age ≥18 years;
• ECOG PS 0-2;
• Histologic diagnosis of colorectal cancer;
• Treatment with fluoropyrimidine plus bevacizumab.

Exclusion Criteria:

• ECOG PS ≥3;
• Absence of histologic diagnosis.