Safety Insights From the CABINET Trial

EP: 1.Understanding Neuroendocrine Tumors in Practice

EP: 2.Treatment Landscape for Advanced NETs

EP: 3.Evolving Needs in Advanced NET Care

EP: 4.Cabozantinib in Context – CABINET Rationale and Trial Design

EP: 5.Interpreting the Clinical Efficacy of Cabozantinib in NETs

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EP: 6.Safety Insights From the CABINET Trial

EP: 7.Integrating Cabozantinib Into the NET Treatment Landscape

EP: 8.Managing NET Patients on Cabozantinib – Practical Insights

EP: 9.Looking Ahead: The Future of Care for NETs

The safety profile of cabozantinib in the CABINET trial was consistent with what has been seen in other tumor types, such as renal cell carcinoma and hepatocellular carcinoma, where the drug is already approved. The study initiated treatment at a 60-mg dose, but the average dose patients actually received was closer to 40 mg due to common toxicities requiring dose reductions. Fatigue, diarrhea, hypertension, and palmar-plantar erythrodysesthesia (PPE, or hand-foot syndrome) were among the most frequently reported adverse effects. While many of these toxicities were low-grade, they were still clinically impactful, particularly PPE, which can significantly affect patients’ daily functioning. Grade 3 toxicities, such as cytopenias and transaminitis, were relatively infrequent, but their occurrence was notable, especially in patients who had received prior therapies like peptide receptor radionuclide therapy (PRRT).

Importantly, the tolerability of cabozantinib after PRRT raised some concerns. Clinicians reported increased rates of cytopenias, particularly thrombocytopenia, which appeared more frequently than in other tumor types like hepatocellular cancer. This was attributed to cumulative marrow suppression from multiple prior therapies. The study emphasized that while cabozantinib’s adverse effect profile aligns with those of other tyrosine kinase inhibitors (TKIs) such as sunitinib, its use in heavily pretreated NET patients—especially post PRRT—requires careful attention to blood counts and dose management. These insights are especially relevant as many NET patients now receive multiple lines of systemic therapy before reaching TKIs like cabozantinib.

To address these safety concerns and improve tolerability, clinical trials are underway investigating alternate dosing strategies. One such trial is exploring a dose-optimization approach starting at 40 mg and titrating upward to 60 mg based on patient tolerance, rather than the traditional dose-reduction model. This mirrors strategies used with other TKIs, such as regorafenib, and reflects a growing consensus that personalized dosing may offer better long-term outcomes. Most clinicians currently favor starting at 40 mg, then adjusting as tolerated.