What question did this study set out to answer?

To assess the efficacy of cabozantinib in treating high-grade neuroendocrine neoplasms after prior treatments.

May 29, 2026

Cabozantinib in high-grade neuroendocrine neoplasms.

Key Points

To assess the efficacy of cabozantinib in treating high-grade neuroendocrine neoplasms after prior treatments.
Single institution, Phase II study
Patients with HG-NENs who had progressed on at least one prior treatment
CABO administered at 60 mg po daily in 3-week cycles
Median progression free survival (PFS) was 4.01 months (95% CI 1.61 to 9.30)
Median overall survival (OS) was 9.89 months (95% CI 6.73 to 18.96)
Partial response observed in 9.3% of patients, while stable disease was noted in 59.4% (disease control rate 68.8%)

Abstract

4183 Background: High grade neuroendocrine neoplasms (HG-NENs) are treated with platinum doublets mirroring guidelines for small cell lung cancer (SCLC) but recurrences are common and salvage options are limited in efficacy. Cabozantinib (CABO), an inhibitor of VEGFR, MET, and TAM kinases (TYRO3, AXL, and MER) was approved by the FDA for treatment of well differentiated (WD) NENs of both pancreatic and extrapancreatic origins based on the CABINET study (Chan, NEJM 2025). However, its efficacy in the whole spectrum of HG-NEN patients including poorly differentiated disease (PDD) has not been prospectively explored. Methods: This was a single institution, Phase II study of CABO in patients with HG-NENs who had progressed on at least one prior treatment. Key inclusion/exclusion criteria were NENs of any origin except SCLC, high grade by Ki-67 of > 20% or histology consensus, ECOG of 70%. Histology was WD-HG in 40% of patients and PDD in 60%. Two patients had mixed PDD/other components (MiNEN). Median PFS in evaluable patients was 4.01 months 95% CI 1.61 to 9.30 and mOS was 9.89 mo 95% CI 6.73 to 18.96. Three patients so far (9.3%) have had partial response as best response (PDD-colon, WD-pancreas and PDD-cervical) while 19/32 (59.4%) patients have had stable disease as best response so far (disease control rate 68.8%). Five (15.6%) patients have received more than 10 treatment cycles. The three longest treated patients had WD-pancreas (23 and 17 cycles) and PDD-unknown (12 cycles). One patient had eventual resection of a metastatic site and is currently without evidence of disease. Three patients withdrew from the trial because of toxicities (shortness of breath, GI bleeding, thromboembolism). Twenty-six patients have expired. Conclusions: CABO monotherapy showed efficacy in some HG-NEN patients with not just WD but also the very aggressive PDD histology. No new side effects to the ones previously described for this agent were noted. Supported by Exelixis and a Siteman investment program grant. Clinical trial information: NCT04412629 .

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