Sequencing Regorafenib After Fruquintinib Improves OS in mCRC

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Sequencing fruquintinib (Fruzaqla) before regorafenib (Stivarga)demonstrated superior clinical outcomes compared with the reverse sequence for the late-line treatment of patients with metastatic colorectal cancer (CRC), according to data from a subgroup analysis presented during the 2025 AACR Annual Meeting.¹

At the March 1, 2025, data cutoff, patients who received fruquintinib then regorafenib (FR) in the overall population (n = 35) experienced a median overall survival (OS) of 21.2 months compared with 15.8 month in patients who received regorafenib then fruquintinib (RF; n = 18; log-rank P = .587). Additionally, patients in the FR group who received combination therapy (n = 17) achieved a median OS of 23.6 months vs 12.3 months in the RF group (n = 11; log-rank P = .167). The median OS among patients in the third line of treatment was 21.2 months vs 17.7 months in the FR (n = 34) and RF (n = 15) groups, respectively (log-rank P = .571).

“In the management of metastatic CRC, the selection of optimal treatment regimens, particularly when considering sequential therapies, is crucial for improving patient outcomes,” the study authors wrote in a poster presentation of the data. “This study [aimed to compare the [efficacy] of fruquintinib sequential regorafenib [vs] regorafenib sequential fruquintinib in [the] late-line treatment of [patients with] metastatic CRC.”

In November 2023, the FDA approved fruquintinib for the treatment of adult patients with metastatic CRC who previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.²

Diving Into the Study Design and Baseline Characteristics

The study included adult patients with histologically confirmed metastatic CRC.¹ Patients were also required to have an ECOG performance status of 0 or 1 and have received at least 2 prior lines of standard therapy. Eligible patients received either FR or RF therapy.

At baseline, the median age in the FR and RF groups was 56 years (range, 32-78) vs 60.5 years (range, 39-71), respectively. Most patients in both groups had RAS wild-type disease (62.86% vs 61.11%) and had metastatic disease in the lung (54.29% vs 61.11%), liver (71.43% vs 72.22%), and/or multiple sites (77.14% vs 72.22%). All patients in both groups had BRAF wild-type disease and most patients in both groups received prior bevacizumab (Avastin; 80.0% vs 66.67%).

The primary end point was median OS. Secondary end points included median progression-free survival (PFS) and safety.

Additional Efficacy Findings

Additional data demonstrated that fruquintinib before sequential therapy led to a median PFS of 4.4 months compared with 3.7 months for regorafenib in the overall population (P = .014). In the combination therapy population, the median PFS was 7.3 months vs 3.7 months, respectively (P = .035). The overall response rate for fruquintinib before sequential therapy in the overall population was 11.43% compared with 0% for regorafenib. The respective disease control rates were 82.86% and 11.11%. Data from a subgroup analysis revealed that FR therapy led to a median OS benefit vs RF treatment in most evaluated patient subgroups.

“In the late-line treatment of [patients with] metastatic CRC, the sequencing strategy of initial fruquintinib followed by regorafenibmay demonstrate superior clinical outcomes compared [with] the reverse sequence, especially in [the] combination therapy population or in the third-line [of] treatment,” the study authors wrote in their conclusion. “[Our] sample size was relatively limited. [The] sample size should be increased to further validate [these] findings.”

Disclosures: All authors declared no conflicts of interest.

Reference

1. Wangxia L, Liu B, Feng T, et al. A multi-cohort study of treatment regimens for metastatic colorectal cancer (mCRC): subgroup analysis of sequential therapy between fruquintinib and regorafenib. Presented at: 2025 AACR Annual Meeting; April 25-30, 2025; Chicago, IL. Abstract CT085.
2. FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. November 8, 2023. Accessed April 29, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer