Stivarga (regorafenib) / Amgen, Bayer - LARVOL DELTA

Synergistic Therapeutic Outcomes of FAP-Targeted Radiopharmaceutical Therapy with 177Lu-, 90Y-, and 225Ac-Labeled 3BP-3940 in Combination with Immunothery, Chemotherapy and other Targeted Therapies for Sarcoma Patients (SNMMI 2025) - "Previous targeted therapies included mTOR inhibitors (everolimus, tacrolimus; n=1), Pazopanib (n=2), lenvatinib (n=1), and multikinase inhibitors (regorafenib, abemaciclib; n=1). Concurrent targeted therapies included cabozantinib (n=1), trabectenid (n=1), anlotinib (n=1), pazopanib (n=1), and abemaciclib (n=1)...One leiomyosarcoma patient receiving concurrent trabectedin exhibited G4 AP and G3 GT, and the cardiac synovial sarcoma patient on pazopanib had G3 AP and suffered heart failure attributed to pazopanib before the first FRT cycle... FAP-targeted FRT with 177Lu-, 90Y-, and 225Ac-labeled 3BP-3940 demonstrated a favorable safety profile and well-tolerated in sarcoma patients when administered alongside ongoing targeted therapies, showing encouraging signs of efficacy in this small cohort. These findings suggest that combining FRT with immunotherapies or targeted agents may offer better outcomes than either modality alone. Larger prospective studies are needed to..."

Clinical • Combination therapy • IO biomarker • Cardiovascular • Congestive Heart Failure • Heart Failure • Hepatocellular Cancer • Leiomyosarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Synovial Sarcoma • IL2

Case Report WIN-MTB-2023001 WIN International Molecular Tumor Board A 62-year-old male with metastatic colorectal cancer with 5 prior lines of treatment. (PubMed, Oncotarget) - "We present a 62-year-old male with mCRC harboring BRAF, MET, APC, TP53 and NRAS alterations, following FOLFOX and FOLFIRI, dabrafenib plus panitumumab, and a BRAF inhibitor clinical trial, each leading to initial responses followed by disease progression...Personalized combinations suggested included amivantamab-vmjw (anti-MET/EGFR antibody) (one-third standard dose) (for MET amplification and due to prior response to anti-EGFR antibody), trametinib, 1 mg po daily (MEK inhibitor for BRAF V600E mutation), and regorafenib (may have WNT inhibitor activity relevant to APC mutation; VEGFR activity relevant since TP53 alterations upregulate VEGF/VEGFR axis) starting at 40 mg po daily three weeks on, one week off. Another option was trametinib at 1 mg daily, cetuximab (EGFR antibody), 250 mg/m² IV every two-weeks, and cabozantinib (MET and VEGFR inhibitor), 40 mg po daily. FOLFOXFIRI combined with bevacizumab, or liver-directed therapies for hepatic metastases, or..."

Biomarker • Journal • Colorectal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • APC • NRAS • TP53

Efficacy and safety of regorafenib plus biweekly trifluridine/tipiracil for refractory metastatic colorectal cancer: a multicenter single-arm phase II trial. (PubMed, Oncologist) - P4 | "(ClinicalTrials.gov Identifier: ChiCTR2300071752. IRB Approved: KYLL-202203-026-1.)."

Journal • P2 data • Cardiovascular • Colorectal Cancer • Hematological Disorders • Hypertension • Neutropenia • Oncology • Otorhinolaryngology • Solid Tumor • Thrombocytopenia

Correlation between Survival Outcomes and Duration of Sequential Treatment with Regorafenib and Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: Results from the Multicenter Retrospective ReTrITA Study (ESMO-GI 2025) - No abstract available

Metastases • Retrospective data • Colorectal Cancer • Oncology • Solid Tumor

Dose escalation STRATegy of regorafenib in Advanced HepatoCellular Carcinoma: phase II STRATA-HCC trial (ESMO-GI 2025) - No abstract available

Metastases • P2 data • Hepatocellular Cancer • Oncology • Solid Tumor

Trifluridine/tipiracil plus bevacizumab (TTB) versus regorafenib (R) in refractory advanced colorectal cancer patients: a Real-Word Evidence efficacy study. (ESMO-GI 2025) - No abstract available

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor

The use of regorafenib in cholangiocarcinoma. A real-world data (RWD) review (ESMO-GI 2025) - No abstract available

Clinical • Real-world • Real-world evidence • Review • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

Mitigating the Oncogenic Roles of miR-629-5p and miR-660-5p Through Direct Binding by Two Potential Drug Targets for Colorectal Cancer Prevention. (PubMed, Int J Prev Med) - "Additionally, this research examines the efficacy of Regorafenib and 3,3'-diindolylmethane (DIM) as therapeutic agents aimed at mitigating the oncogenic activities of these miRNAs by influencing their structural and conformational dynamics, thereby offering a preventive strategy against CRC...They indicated a high affinity to miRNA-629-5p compared with miRNA-660-5p created a slight change in its structure and can suppress its activity in CRC. However, extra experimental approaches are needed to approve our hypothesis."

Journal • Colorectal Cancer • Oncology • Solid Tumor • MIR660

Targeting USP18 overcomes acquired resistance in hepatocellular carcinoma by regulating NCOA4 deISGylation and ferroptosis. (PubMed, Cell Death Dis) - "Importantly, we screened and identified hyperoside (HYP) as a new USP18 enzyme activity inhibitor, which sensitizes cancer cells to existing targeted therapies (sorafenib and regorafenib) by inhibiting USP18 and following deISGylation of NCOA4. Collectively, our study has uncovered a novel mechanism of acquired sorafenib resistance and offers a promising combination therapy strategy for overcoming therapeutic resistance in HCC."

Journal • Preclinical • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • NCOA4 • STING • USP18

DHODH blockade induces ferroptosis in neuroblastoma by modulating the mevalonate pathway. (PubMed, Mol Cell Proteomics) - "To address this challenge, we employed virtual screening to discover potential DHODH-targeting drugs, identifying Regorafenib as a promising candidate...In summary, our study highlights DHODH blockade as a novel approach to induce ferroptosis through lipid metabolism reprogramming, underscoring DHODH as a viable therapeutic target for neuroblastoma treatment. These insights open new avenues for metabolic-based interventions in aggressive pediatric cancers."

Journal • Metabolic Disorders • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • SQLE

The efficacy and safety of regorafenib/fruquintinib combined with PD-1/PD-L1 for metastatic colorectal cancer: a meta-analysis based on single-arm studies. (PubMed, Front Immunol) - "These findings offer new insights for treating mCRC, although they should be validated through large randomized controlled trials. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024582268."

Clinical • Journal • Retrospective data • Review • Colorectal Cancer • Oncology • Solid Tumor • PD-1 • PD-L1

5-Fluorouracil/Leucovorin (5FU/LV) in Combination With Regorafenib in Patients With Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=56 | Recruiting | Sponsor: The Methodist Hospital Research Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor

Real-world evidence of fruquintinib (Fruq) efficacy after regorafenib (Rego) and trifluridine–tipiracil (TAS-102) in refractory metastatic colorectal cancer (mCRC). (ASCO 2025) - " This retrospective, multi-site cohort study evaluated outcomes in 33 mCRC pts who received Fruq following treatment with Rego and/or TAS-102 with or without bevacizumab. This real-world analysis highlights the clinical benefit of Fruquintinib in mCRC patients following treatment with Regorafenib and/or TAS-102. The data suggest flexibility in treatment choices, with Fruquintinib showing improved OS when used earlier in the treatment sequence. These findings underscore the importance of exploring optimal sequencing strategies and evaluating Fruquintinib as a potential option before other approved agents in the refractory setting."

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Colorectal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • BRAF

Cardiovascular toxicity of fruquintinib in patients with colorectal and other cancers: A systematic review and meta-analysis. (ASCO 2025) - "Compared to Regorafenib, Fruquintinib demonstrated an OR of 1.549 (95% CI: 0.804, 2.983; P = 0.191) for the development of hypertension. Our study found that Fruquintinib is associated with significant cardiovascular risks, with hypertension being the most common adverse event, while thromboembolism did not reach statistical significance. Therefore, close monitoring for treatment-related cardiovascular events should be considered in these patients."

Retrospective data • Review • Cardiovascular • Colorectal Cancer • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Hypertension • Oncology • Peripheral Arterial Disease

Evaluating the efficacy of fruquintinib versus regorafenib and trifluridine/tipiracil in treating advanced metastatic colorectal cancer: A match-adjusted indirect comparison. (ASCO 2025) - P3 | "Our analyses showed favorable OS and PFS for fru versus reg and TAS102, as well as beneficial PFS in male versus reg, in K-Ras wild-type subgroup versus reg and TAS102, along with superior OS in < 65 years subgroup versus TAS102, highlighting its therapeutic potential in treating patients with previously treated mCRC. Limitations include the inability to adjust all covariances, biases due to unobserved covariances, and lacking comparison between reg and TAS102 due to unavailable IPDs. The findings should be validated through future RWS."

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor • KRAS • RAS

Navigating third-line therapies: A comprehensive review of regorafenib versus fruquintinib with placebo comparator for metastatic colorectal cancer—A systematic review and meta-analysis. (ASCO 2025) - "Regorafenib and Fruquintinib offer similar clinical benefits in refractory mCRC, but Fruquintinib may have a more favorable toxicity profile, particularly for all-grade adverse events. These findings suggest that Fruquintinib could be a preferred option based on tolerability, though both agents remain essential therapeutic options in advanced mCRC."

Metastases • Retrospective data • Review • Colorectal Cancer • Oncology • Renal Disease • Solid Tumor

Overall survival with fruquintinib versus placebo after adjusting for subsequent anticancer therapy in patients with refractory metastatic colorectal cancer in the FRESCO-2 study. (ASCO 2025) - P3 | "Eligible patients had received prior chemotherapy, anti-VEGF therapy, anti-EGFR therapies (if indicated), and TAS-102 and/or regorafenib...Among these patients, the most common subsequent anticancer therapies in the fruquintinib vs placebo arms were fluorouracil (7.7% vs 9.6%) and regorafenib (7.5% vs 7.8%)... Consistent with the primary analysis of the FRESCO-2 intent-to-treat population, fruquintinib improved overall survival vs placebo after adjusting for the impact of subsequent anticancer therapy. Furthermore, these analyses are robust with consistent results reported using IPCW and MSM. These findings support fruquintinib as a new treatment option for patients with previously treated mCRC."

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor

A multi-cohort real-world study of treatment for metastatic colorectal cancer (mCRC): Overall efficacy analysis and subgroup analysis of previous bevacizumab use or not. (ASCO 2025) - "Funded by No funding sources reported Background: Fruquintinib (Fru) is a VEGFR1/2/3 inhibitor and has been approved in USA for third-line treatment of mCRC based on FRESCO-2 data. Regorafenib (Reg) and TAS-102 have shown promise in mCRC treatment... The results suggest that Fru-based regimens, particularly in combination with ICIs, may offer survival benefits compared to standard regimens, especially in patients without prior Bev use."

Clinical • Metastases • Real-world • Real-world evidence • Colorectal Cancer • Oncology • Solid Tumor • FLT1

Telisotuzumab adizutecan (ABBV-400; Temab-A) monotherapy vs trifluridine/tipiracil plus bevacizumab in patients with refractory metastatic colorectal cancer with increased c-Met protein expression: An open-label, randomized, phase 3 trial. (ASCO 2025) - P1, P3 | "Patient eligibility includes age ≥18 years, confirmed c-Met expression of 3+ in ≥10% of tumor cells, metastatic adenocarcinoma of the colon/rectum, measurable disease per RECIST v1.1, ECOG performance status 0–1, prior treatment with a fluoropyrimidine (eg, 5-FU or capecitabine), oxaliplatin, irinotecan, and an anti-VEGF antibody (unless locally not approved) or an anti-EGFR antibody if indicated, and appropriate targeted therapy or immunotherapy if targetable mutations present (eg, BRAF V600E or HER2) or MSI-H/dMMR. Prior treatment with regorafenib and/or fruquintinib is permitted, but no prior treatment with trifluridine/tipiracil Study-specific c-Met protein expression IHC cutoff is defined as 3+ intensity in ≥10% of tumor cells...Safety evaluations include adverse event monitoring, vital sign measurements, ECG variables, and clinical laboratory testing. Enrollment began in December 2024."

Clinical • IO biomarker • Metastases • Monotherapy • P3 data • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • HER-2 • MET • MSI

Rechallenge with epidermal growth factor receptor inhibitors for metastatic colorectal cancer: A systematic review and meta-analysis. (ASCO 2025) - "In 20 studies, EGFRi rechallenge was given only to patients previously progressing on 5-fluoropyrimidine, oxaliplatin or irinotecan...The pooled ORR was 15% (95% CI, 9%-24%) which is numerically higher than that achieved by FDA-approved third-line agents (trifluridine/tipiracil plus bevacizumab 6.1%, fruquintinib 2%, and regorafenib 1.5%)... EGFRi rechallenge is associated with a significantly longer PFS, numerically longer OS and clinically meaningful ORR as compared with EGFRi-free systemic therapy in patients with heavily-pretreated mCRC, particularly for patients with pre-rechallenge RAS/RAF-wild type mCRC."

Metastases • Retrospective data • Review • Colorectal Cancer • Oncology • Solid Tumor • EGFR

Phase Ⅱ Clinical Trial of Cadonilimab Combined With Anti-angiogenic Agents in Metastatic dMMR/MSI-H CRC (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Fudan University

dMMR • MSI-H • New P2 trial • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor

Real-world experience of fruquintinib in patients with metastatic colorectal cancer: A single-center retrospective study in the United States. (ASCO 2025) - "This study provides real-world insights into fruquintinib use in the United States, including patients with poor performance status. The safety profile was consistent with the FRESCO-2 study, though patients with ECOG > 1 experienced greater toxicity. Efficacy appeared lower in those previously treated with regorafenib."

Metastases • Real-world • Real-world evidence • Retrospective data • Anorexia • Colorectal Cancer • Dermatology • Fatigue • Hypertension • Oncology • Solid Tumor

Toxicity profile of fruquintinib (Fruq) versus regorafenib (Rego) in refractory metastatic colorectal cancer (mCRC). (ASCO 2025) - "Compared to Rego, Fruq showed a more favorable toxicity profile in all TRAEs except in HTN where Fruq had a higher risk. This review emphasizes the need for direct head-to-head comparisons between Fruq and Rego in experimental settings."

Metastases • Cardiovascular • Colorectal Cancer • Fatigue • Hypertension • Oncology • Solid Tumor

An observational/translational study to conduct real-world evidence and develop biomarkers of fruquintinib for patients with metastatic colorectal cancer (mCRC): FruBLOOM trial (JACCRO CC-19). (ASCO 2025) - P=N/A | "The FRESCO-2 trial was conducted in patients (pts) treated with FTD/TPI and/or regorafenib (Rego) and did not include pts who were not using either agent. Although FTD/TPI + bevacizumab (Bev) is currently one of 3rd-line standard treatments for mCRC, there are few data regarding the efficacy and safety of FRU in pts after FTD/TPI + Bev...We will enroll 200 pts receiving FRU after FTD/TPI + Bev to the cohort A, and 100 pts receiving FRU as 3rd-line or after both FTD/TPI + Bev and Rego to the cohort B. Eligibility criteria are (1) pts with CRC confirmed as adenocarcinoma, (2) pts planning to receive FRU monotherapy as 3rd- or later-line treatment, (3) prior treatments with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, an anti-EGFR therapy (if RAS/BRAF wild-type), BRAF therapy (if BRAF mutant), and immune checkpoint inhibitor (if MSI-high), (4) pts with ECOG Performance Status of 0-2, (5) pts must be at least 18..."

Biomarker • Clinical • HEOR • IO biomarker • Metastases • Real-world • Real-world evidence • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Overall survival based on sequencing of fruquintinib, regorafenib, and TAS-102 with or without bevacizumab in treatment-refractory metastatic colorectal cancer. (ASCO 2025) - "Funded by No funding sources reported Background: Fruquintinib, regorafenib, and trifluridine-tipiracil (TAS-102) alone or in combination with bevacizumab (bev) are approved for use in treatment of metastatic colorectal cancer (mCRC) following progression on or intolerance to fluoropyrimidine-based therapy with irinotecan, oxaliplatin, and targeted agents if indicated. Fruquintinib sequenced after TAS-102 +/- bev may confer an OS advantage in the treatment of mCRC. However, prospective studies evaluating sequencing strategies representative of standard prescribing patterns are still needed to firmly establish optimal sequencing of fruquintinib, regorafenib, and TAS-102-based therapy."

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor