Cabozantinib for Pretreated Patients With Advanced Neuroendocrine Tumors: CABINET Trial

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The Alliance for Clinical Trials in Oncology announced detailed results from CABINET (Alliance A021602), a phase III pivotal trial evaluating cabozantinib compared with placebo in two cohorts of previously treated patients with neuroendocrine tumors. The data were presented by Chan et al at the ESMO Congress 2023 (Abstract LBA53).

One cohort consisted of patients with advanced pancreatic neuroendocrine tumors (pNET); the second cohort included patients with advanced extrapancreatic neuroendocrine tumors (epNET). The study met the primary objective for each cohort, demonstrating that cabozantinib provided improvements in median progression-free survival for the patients in both the pNET and epNET cohorts.

“Although progress has been made in recent years, there remains a critical need for new and effective therapies for patients with advanced neuroendocrine tumors. Given that there is no standard treatment for patients with progressive disease, these results showing notable improvements in progression-free survival are highly encouraging for patients and their physicians,” said Alliance Study Chair Jennifer Chan, MD, MPH, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute. “I am pleased to present these important findings at [the ESMO Congress 2023], as they underscore the potential of cabozantinib as a much-needed new treatment option for this disease, which is rising in incidence.”


CABINET is a multicenter, randomized, double-blinded, placebo-controlled phase III pivotal trial. As of June 2023, this trial enrolled 290 patients in two separate cohorts (pNET, n = 93; epNET, n = 197) in the United States, and they were included in the analyses reviewed by the Alliance Data and Safety Monitoring Board (DSMB). Patients were randomly assigned 2:1 into the cabozantinib or placebo arms of the study in each of the two cohorts.

Patients must have had measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and must have experienced disease progression after at least one U.S. Food and Drug Administration–approved line of prior therapy other than somatostatin analogs. For patients with advanced neuroendocrine tunors, treatment options include somatostatin analogs; targeted therapy with lutetium Lu-177 dotatate, which is a form of peptide-receptor radionuclide therapy; or chemotherapy. More than half of the patients in each cohort received prior treatment with everolimus or prior Lu-177 dotatate.

The primary endpoint was progression-free survival in each cohort. Upon confirmation of disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with cabozantinib. Secondary endpoints included overall survival, radiographic response rate, and safety.

In August, the Alliance DSMB recommended the study stop and be unblinded early due to the improvement in efficacy observed at an interim analysis. The DSMB based their vote on data from interim analyses of progression-free survival using local radiology assessments. Ancillary analyses were conducted using local and central assessments of patients enrolled through June 2023.

Updated Results Presented at ESMO

Results from the CABINET study presented at the ESMO Congress 2023 demonstrate that treatment with cabozantinib resulted in improvements in progression-free survival based both on local review and on independent blinded central radiology review. At a median follow-up of 13.9 months, the median progression-free survival for patients with epNET who took cabozantinib was 8.3 months, compared to 3.2 months for those who took placebo. At a median follow-up of 16.7 months, patients with pNET who took cabozantinib had a median progression-free survival of 11.4 months, compared to 3 months for those who took placebo.

The safety profile of cabozantinib observed in each cohort was consistent with those found in other studies of the drug. Reported adverse events included hypertension, fatigue, diarrhea, and rash. No new safety signals were identified.

“The CABINET trial is a great example of the importance of the National Clinical Trials Network, sponsored by the National Cancer Institute, in conducting rigorous, practice-changing trials at both academic and community oncology practices throughout the United States, working with industry partners, patient advocacy, and academia,” noted Eileen O’Reilly, MD, of Memorial Sloan Kettering Cancer Center, and Jeffrey Meyerhardt, MD, MPH, of Dana-Farber Cancer Institute, who co-chair the Gastrointestinal Committee for the Alliance.

Disclosure: CABINET is sponsored by the National Cancer Institute (NCI) and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded national clinical trials network (NCTN) as part of Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP). For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.