Compared with placebo, Cabometyx (cabozantinib) improved progression-free survival (PFS) after progression on prior therapy for extrapancreatic neuroendocrine tumors (NETs) with a primary tumor arising in the gastrointestinal (GI) tract, as demonstrated in subgroup data from the CABINET trial presented at the 2025 Gastrointestinal Cancers Symposium.
The VEGF-targeted agent also improved PFS versus placebo in patients with various clinical factors, except in those with a primary site of a non-midgut GI tumor.
Findings from the analysis revealed that patients in the extrapancreatic NET cohort with a primary tumor arising in the GI tract (116 patients) experienced a median PFS of 8.5 months in the Cabometyx arm (70 patients) versus 5.6 months in the placebo arm (46 patients). Best overall responses in the Cabometyx and placebo arms included confirmed partial response (1% versus 0%), stable disease (69% versus 65%) and progressive disease (9% versus 26%), and patients were also not evaluable (21% versus 9%), respectively.
“New therapeutic options are needed for patients with advanced NETs,” Dr. Jonathan Strosberg, leader of the Neuroendocrine Tumor Division and Department of Gastrointestinal Oncology Research Program at Moffitt Cancer Center in Tampa, Florida, wrote in a poster presentation of the findings. “Potential benefit was observed across clinical factors including grade, functional status, [use] concurrent somatostatin analogs and prior treatment.”
Prior data from CABINET showed that Cabometyx significantly improved PFS versus placebo in patients with previously treated, progressive advanced extrapancreatic or pancreatic NETs. Confirmed objective response rates were 5% and 19% in patients with extrapancreatic and pancreatic NETs, respectively.
GIossary:
Progression-free survival: the time during and after treatment when a patient with cancer is alive without the disease worsening.
Best overall response: the best result seen during the treatment period in terms of how the cancer responded to the treatment.
Objective response rate: the percentage of patients with a complete or partial response to treatment within a period of time.
ECOG performance score of 1 or 2: the patient is able to walk and do light activities but cannot do strenuous activities, or they are able to take care of themselves but unable to work.
Patients enrolled in CABINET had grade I to III well to moderately differentiated NETs and had experienced disease progression within 12 months prior to random assignment following treatment with at least one prior FDA-approved systemic therapy, not including somatostatin analogs. They were then assigned to the extrapancreatic NET arm or pancreatic NET arm and randomly assigned to receive Cabometyx or placebo. The main focus of the trial was to assess PFS.
Baseline Patient Characteristics From the Subgroup Analysis
The median number of prior systemic therapies received, not including somatostatin analogs, was one in both the Cabometyx and placebo arms. All patients had received somatostatin analogs previously, and most had received Afinitor (everolimus; 61% versus 54%) or Lutathera (lutetium Lu 177 dotatate; 79% versus 74%), and some were given Temodar (temozolomide)–based therapies (17% versus 15%).
The median duration of therapy was 5.8 months among patients treated with Cabometyx (68 patients) and 3.7 months among those given placebo (45 patients). Additionally, 13 versus 7 patients remained on treatment in the respective arms. Reasons for discontinuation included progressive disease, side effects, withdrawn consent and death on study.
Additional Findings and Safety
Cabometyx yielded a PFS benefit versus placebo among all clinical factor groups examined in this subgroup analysis aside from in those with a primary tumor site of non-midgut GI. The most pronounced benefit was seen in those who had not received prior Lutathera, had grade I disease, had an ECOG performance score of 1 or 2 and who had a primary tumor site of midgut GI.
The safety profile of Cabometyx was consistent with previously reported data, and in this patient population treated with the agent (68 patients) versus placebo (45 patients), grade 3 (severe) to 4 (life-threatening) side effects occurred in 60% versus 18% of patients. Notable grade 3 to 4 side effects included hypertension (19% versus 4%), diarrhea (13% versus 4%) and fatigue (10% versus 4%), respectively. Grade 5 (death) toxicities that may have been related to study treatment occurred in three patients treated with Cabometyx; one patient experienced cardiac arrest, and the other two causes of death were not specified.
Reference:
“Efficacy and safety of cabozantinib for advanced gastrointestinal (GI) neuroendocrine tumors (NET) after progression on prior therapy: subgroup analysis of the phase 3 CABINET trial (Alliance A021602).” By Dr. Jonathan Strosberg, et al. Presented at: 2025 Gastrointestinal Cancers Symposium; 2025 Jan 16-18; San Francisco, CA. Abstract 666
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