Neoadjuvant Treatment With Regorafenib and Capecitabine Combined With Radiotherapy in Locally Advanced Rectal Cancer:...

Area of Science:

• Oncology
• Gastroenterology
• Pharmacology

Background:

• Regorafenib, a multi-tyrosine kinase inhibitor, demonstrates activity in metastatic colorectal cancer.
• Investigating the efficacy of adding regorafenib to long-course chemoradiotherapy (LcCRT) in molecularly undefined locally advanced rectal cancer (LARC).

Purpose of the Study:

• To evaluate the safety and efficacy of neoadjuvant LcCRT with regorafenib in patients with LARC.
• To determine the recommended dose (RD) of regorafenib and assess pathological response rates.

Main Methods:

• Phase I/II trial including patients with T3-4 and/or N+ M0 rectal cancer.
• Neoadjuvant LcCRT with capecitabine and radiation, with regorafenib dose escalation (40, 80, 120 mg) followed by an expansion cohort at the RD (80 mg).
• Primary endpoints: dose-limiting toxicity (DLT) for dose escalation and pathological response (near-complete regression [npCR] or complete regression [pCR]) for expansion.

Main Results:

• The RD of regorafenib was established at 80 mg daily due to DLTs at 120 mg.
• In the expansion cohort (n=19), 42.1% achieved the primary endpoint (npCR: 26.3%, pCR: 15.8%).
• R0 resection rates were 100%; common grade ≥3 adverse event was diarrhea (2 patients).

Conclusions:

• Adding regorafenib 80 mg to LcCRT in LARC met primary endpoints for pathological response and toxicity.
• The combination demonstrated manageable toxicity and expected postoperative complication rates.
• This regimen shows potential for improving clinical outcomes in LARC patients.