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