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Regorafenib (Stivarga) in combination with trifluridine/tipiracil (Lonsurf; TAS-102) displayed promising efficacy with a manageable safety profile in patients with pretreated metastatic colorectal cancer (CRC), according to data from the phase 2 REGTAS study (ChiCTR2300071752) published in the Oncologist.1
Efficacy-evaluable patients who received the combination (n = 24) experienced a median progression-free survival (PFS) of 4.9 months (95% CI, 4.0-5.8) and a median overall survival (OS) of 15.4 months (95% CI, 11.0-19.9). The overall response rate (ORR) was 8.3% (95% CI, 2.3%-25.8%); all responses were partial. The disease control rate (DCR) was 83.3% (95% CI, 64.1%-93.3%).
“This trial studying the combination of regorafenib and biweekly trifluridine/tipiracil offers a new avenue for the treatment of [patients with] refractory metastatic CRC. This approach provided promising benefits in terms of DCR, PFS, and OS,” the study authors wrote.
REGTAS was a single-arm, multicenter Chinese study that enrolled adult patients with histologically confirmed microsatellite stable, unresectable metastatic CRC. Eligible patients were required to have a World Health Organization performance status of 0 or 1, a life expectancy of at least 3 months, and measurable lesions per RECIST 1.1 criteria. Those who received prior trifluridine/tipiracil or a TKI, had unstable cardiac disease, or had a history of arterial or venous thrombotic or embolic events within 6 months of enrollment were excluded.
Prior lines of treatment needed to include fluoropyrimidine, irinotecan, oxaliplatin, and bevacizumab (Avastin). Patients with RAS wild-type disease were permitted to have received an anti-EGFR antibody.
Patients received regorafenib at 120 mg daily for 21 days via 4-week cycles or at 80 mg daily followed by a weekly increase of 40 mg up to 120 mg per day. Trifluridine/tipiracil was administered at 30 mg/m2 twice daily on days 1 through 5 of a biweekly dosing schedule.
The primary end point was PFS. Secondary end points included ORR, DCR, OS and safety.
At baseline, the median age in the overall population (n = 28) was 58 years (range, 33-73). Most patients received 2 prior lines of therapy (n = 25), had an ECOG performance status of 1 (n = 17), had a primary tumor of the rectum (n = 15), had RAS-mutated disease (n = 15), and had lung and/or liver metastases (n = 16). Beyond the required prior therapies, 11 patients received previous cetuximab (Erbitux) and 1 was previously treated with a G12C inhibitor.
Additional findings from REGTAS revealed that the median PFS for patients with (n = 12) and without (n = 12) liver metastases was 4.4 months and 5.1 months, respectively (HR, 1.19; 95% CI, 0.50-2.81; P = .695). Patients with RAS/BRAF-mutated disease (n = 14) experienced a median PFS of 4.9 months compared with 4.3 months among those with wild-type disease (n = 10; HR, 1.58; 95% CI, 0.65-3.82; P = .309).
In terms of safety, all patients experienced at least 1 any-grade treatment-related adverse effect (TRAE). The most common any-grade TRAEs included hypertension (67.9%), hand-foot skin reaction (60.7%), fatigue (50.0%), and hoarseness (35.7%). The most common grade 3 or higher TRAEs included hypertension (7.1%), neutropenia (7.1%), thrombocytopenia (3.6%), and hoarseness (3.6%). One patient discontinued therapy due to a duodenal fistula that was deemed to be related to treatment with regorafenib. No treatment-related deaths were reported.
“In summary, the REGTAS study suggests that a combination of regorafenib and biweekly trifluridine/tipiracil is a feasible, well-tolerated, and effective treatment option for [patients with] refractory metastatic CRC,” the study authors wrote in their conclusion.
Reference
Wang X, Li Z, Sha D, et al. Efficacy and safety of regorafenib plus biweekly trifluridine/tipiracil for refractory metastatic colorectal cancer: a multicenter single-arm phase II trial. Oncologist. 2025;30(6):oyaf129. doi:10.1093/oncolo/oyaf129