CABINET and STELLAR-303 Trials Inform Treatment in NETs and mCRC
Key Points
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Based on data from the CABINET study, cabozantinib is most often used as a second- or third-line option for patients with neuroendocrine tumors (NETs) who have progressed after somatostatin analogs and peptide receptor radionuclide therapy (PRRT).
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The phase 3 STELLAR-303 trial demonstrated a significant overall survival benefit for the combination of zanzalintinib plus immunotherapy compared with regorafenib in patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC).
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Emerging data suggest VEGF tyrosine kinase inhibitor (TKI)–immunotherapy combinations may overcome traditional resistance seen in colorectal cancer with liver metastases, offering a potential path forward in metastatic disease.
Recent phase 3 clinical trial data are shaping real-world practice for the treatment of patients with NETs and mCRC. Nicholas Hornstein, MD, PhD, of Northwell Health, and Anwaar Saeed, MD, of the University of Pittsburgh, discussed the evolving treatment strategies during an event coinciding with the 2026 ASCO Gastrointestinal (GI) Cancers Symposium.
In NETs, Dr. Saeed uses cabozantinib in line with the CABINET study population, often in the second- or third-line setting after progression on somatostatin analogs and PRRT. Although the FDA-approved dose is 60 mg, she starts patients at 40 mg, which she considers a well-tolerated and practical dose for most patients with NETs.
The STELLAR-303 trial, a large global phase 3 study evaluating zanzalintinib, a VEGF TKI, plus atezolizumab versus regorafenib in previously treated patients with MSS mCRC, shows significant survival advantages. However, the combination therapy is not yet FDA-approved.
Dr. Saeed emphasized that, once approved, the positive findings validate earlier-phase studies and support this approach. She also noted that subgroup analyses from STELLAR-303 suggested that patients with colorectal liver metastases—historically resistant to immunotherapy—may still derive benefit from this combination.
The conversation also highlighted additional practice-relevant data emerging at ASCO GI, including updates from the BREAKWATER study and growing momentum around circulating DNA and minimal residual disease assays.