CABOMETYX Shows Significant Efficacy in Both Functional and Non-Functional Neuroendocrine Tumors
核心洞察
CABOMETYX demonstrated significant improvements in progression-free survival for patients with previously treated advanced neuroendocrine tumors (搜索) regardless of functional status in the phase 3 CABINET trial.
The drug reduced the risk of disease progression or death by 74% in non-functional NET (搜索) and 60% in functional NET compared to placebo.
Median progression-free survival increased threefold in non-functional NET (搜索) (9.4 vs 3.1 months) and more than doubled in functional NET (12.7 vs 5.4 months) compared to placebo.
Exelixis announced compelling results from a subgroup analysis of the phase 3 CABINET pivotal trial, demonstrating that CABOMETYX (cabozantinib) significantly improved progression-free survival in patients with previously treated advanced neuroendocrine tumors (搜索) (NET (搜索)) regardless of whether the tumors were functional or non-functional. The data were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
Substantial Efficacy Across NET Subtypes
The subgroup analysis revealed that CABOMETYX reduced the risk of disease progression or death by 74% in patients with non-functional NET (搜索) and by 60% in patients with functional NET compared to placebo. In patients with non-functional NET, the hazard ratio was 0.26 (95% confidence interval: 0.17-0.41; p<0.001), with median progression-free survival of 9.4 months for CABOMETYX versus 3.1 months for placebo. For functional NET patients, the hazard ratio was 0.40 (95% CI: 0.20-0.82; p=0.012), with median progression-free survival of 12.7 months for CABOMETYX compared to 5.4 months for placebo.
"Patients with hormone-producing tumors may require approaches that not only control tumor growth but also help mitigate challenging hormone-related symptoms," said Nikolaos A. Trikalinos, M.D., Associate Professor of Medicine at Washington University School of Medicine and Siteman Cancer Center. "It is encouraging that our results reinforce cabozantinib as a meaningful treatment option for patients with advanced NET (搜索) regardless of functional status."
Trial Design and Patient Population
The CABINET study enrolled 298 patients with locally advanced or metastatic pancreatic NET (搜索) (pNET) or extra-pancreatic NET (搜索) (epNET), randomized 2:1 in separate cohorts to receive CABOMETYX 60 mg daily versus placebo. Of the total enrollment, 179 patients had non-functional NET (搜索) (123 receiving cabozantinib, 56 receiving placebo), 74 had functional NET (47 receiving cabozantinib, 27 receiving placebo), and 45 had unknown functional status.
The trial was sponsored by the National Cancer Institute and conducted by the NCI-funded Alliance for Clinical Trials in Oncology. Patients were required to have measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one FDA-approved line of prior systemic therapy other than somatostatin analogs.
Safety Profile Remains Consistent
The safety profile of CABOMETYX in both functional and non-functional NET (搜索) patients was consistent with its known safety profile, with no new safety signals identified. The most frequent grade 3/4 adverse events in patients with functional NET were hypertension (21%) and diarrhea (9%), while in non-functional NET patients, they were hypertension (21%) and fatigue (18%).
Clinical Significance for NET Treatment
"Following last year's U.S. and EU approvals of CABOMETYX for the treatment of previously treated advanced NET (搜索), these subgroup findings from the CABINET trial reinforce its ability to delay disease progression for a broad and heterogenous population of these patients," said Dana T. Aftab, Ph.D., Executive Vice President, Research & Development at Exelixis. "CABOMETYX is now the leading oral therapy for previously treated advanced NET, helping to address a significant unmet need for patients who have limited options."
Neuroendocrine tumors (搜索) are cancers that begin in specialized cells of the body's neuroendocrine system, with an estimated 161,000 to 192,000 people in the U.S. living with unresectable, locally advanced or metastatic NET (搜索). Functional NET release peptide hormones that can cause debilitating symptoms like diarrhea, hypertension and flushing, while symptoms of non-functional NET are related primarily to tumor growth.
Future Development Plans
Exelixis is also investigating zanzalintinib, an investigational oral kinase inhibitor, in the ongoing STELLAR-311 pivotal trial to potentially improve outcomes in early-line treatment compared to everolimus. The company remains committed to further improving standards of care for NET (搜索) patients who currently have limited treatment options after disease progression.