CHMP Recommends EU Approval of Cabozantinib for Pancreatic and Extra-Pancreatic Neuroendocrine Tumors

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The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion for cabozantinib (Cabometyx) for the treatment of adult patients with unresectable or metastatic, well-differentiated extra-pancreatic neuroendocrine tumors (epNET) and pancreatic neuroendocrine tumors (pNET) who have progressed after at least 1 prior systemic therapy besides somatostatin analogues.1

The CHMP’s recommendation is based on data from the phase 3 CABINET trial (NCT03375320), which evaluated the efficacy and safety of cabozantinib compared with placebo in 2 cohorts of patients with either advanced epNET or advanced pNET.

In March 2025, the FDA approved cabozantinib for the treatment of adult and pediatric patients 12 years of age or older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pNET and epNET.2 The regulatory decision was supported by data from the CABINET trial.

“Neuroendocrine tumors are difficult to treat given their indolent nature and lack of robust responses to traditional oncology agents. This often results in people living with this type of cancer for long periods of time and running out of effective options, underscoring the critical need for new treatments following disease progression,” Amy Peterson, MD, executive vice president of Product Development and Medical Affairs and chief medical officer of Exelixis, the developer of cabozantinib, said in a news release. “The CHMP’s recommendation is a pivotal milestone for our partner Ipsen as they work to bring [cabozantinib] to patients in Europe, and we look forward to hearing the European Commission’s decision in the coming months.”

Data from the trial, which were published in February 2025 in the New England Journal of Medicine, revealed that in the epNET cohort (n = 203), the median progression-free survival (PFS) was 8.4 months (95% CI, 7.6-12.7) vs 3.9 months (95% CI, 3.0-5.7) with cabozantinib and placebo, respectively (HR, 0.38; 95% CI, 0.25-0.59; P < .001).3 In the pNET cohort (n = 95), the median PFS was 13.8 months (95% CI, 9.2-18.5) vs 4.4 months (95% CI, 3.0-5.9) with cabozantinib and placebo, respectively (HR, 0.23; 95% CI, 0.12-0.42; P < .001). Of note, the incidence of confirmed objective response rate (ORR) was 5% and 19% with cabozantinib in patients with epNET and pNET, respectively, which was compared with 0% in those treated with placebo.

Diving Into the CABINET Trial

The multicenter, randomized, double-blinded, placebo-controlled study enrolled 298 patients with either epNET or pNET in the United States at the final analysis period.1 Patients on the study were randomly assigned 2:1 to receive either cabozantinib at a dose of 60 mg or placebo. Notably, patients in the respective cohorts were randomly assigned separately, and each cohort had its own statistical analysis plan. Following the interim analysis, the trial was stopped early, as it demonstrated superior efficacy with cabozantinib compared with placebo in both cohorts.

Patients included on the study had well- or moderately-differentiated pNET or non-pancreatic NET (carcinoid) pathology, locally advanced/unresectable or metastatic disease, and histologic documentation of NETs located in pancreatic, gastrointestinal, lung, thymus, other, or unknown primary site.4 Target lesions also must have demonstrated evidence of disease progression per RECIST 1.1 criteria in the 12 months before trial registration. Additionally, patients were required to have measurable disease per RECIST 1.1 criteria by CT/MRI, and have previously received and progressed on treatment.

The primary end point of the study was PFS assessed by blinded independent central review. Secondary end points included ORR, overall survival, and safety.

The Safety Profile of Cabozantinib in epNET/pNET

Grade 3 or higher adverse effects (AEs) were observed in 62% to 65% of patients treated with cabozantinib, compared with 23% to 27% of patients who received placebo.3 The most common grade 3 or higher treatment-related AEs included hypertension, fatigue, diarrhea, and thromboembolic events.

References

1. Exelixis’ partner Ipsen receives positive CHMP opinion for Cabometyx (cabozantinib) for patients with previously treated advanced neuroendocrine tumors. News release. Exelixis. June 20, 2025. Accessed June 20, 2025. https://ir.exelixis.com/news-releases/news-release-details/exelixis-partner-ipsen-receives-positive-chmp-opinion-1
2. FDA approves cabozantinib for adults and pediatric patients 12 years of age and older with pNET and epNET. FDA. March 26, 2025. Accessed June 20, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cabozantinib-adults-and-pediatric-patients-12-years-age-and-older-pnet-and-epnet
3. Chan JA, Geyer S, Zemla T, et al. Phase 3 trial of cabozantinib to treat advanced neuroendocrine tumors. N Engl J Med. 2025;392(7):653-665. doi:10.1056/NEJMoa2403991
4. Testing cabozantinib in patients with advanced pancreatic neuroendocrine and carcinoid tumors. ClinicalTrials.gov. Updated June 12, 2025. Accessed June 20, 2025. https://clinicaltrials.gov/study/NCT03375320