GI and Lung NET Cohort Shows PFS Improvement With Cabozantinib

Jason S. Starr, DO, assistant professor of medicine and a hematologist/oncologist in the Department of Internal Medicine at Mayo Clinic, discusses the significance of the extrapancreatic neuroendocrine tumor (NET) cohort of the phase 3 CABINET trial (NCT03375320) of cabozantinib (Cabometyx).

The randomized trial investigated both pancreatic and extrapancreatic NETs, showing benefit for cabozantinib vs placebo in previously treated patients. Starr notes that extrapancreatic NETs most commonly have a primary site in the small bowel or elsewhere in the gastrointestinal (GI) tract, but 20% had lung NETs—sometimes termed lung carcinoids—a disease state in need of more approved therapies.

The median progression-free survival (PFS) was 8.4 months with cabozantinib vs 3.9 months with placebo in the extrapancreatic cohort, showing statistically significant benefit overall and in patients with GI, lung and thymus, and other primary disease sites. As sunitinib (Sutent) is approved for pancreatic but not extrapancreatic NETs, cabozantinib offers a new treatment approach in this cohort.

Additionally, a subgroup analysis reported subsequent to the primary results for the lung/thymus subgroup showed an even greater benefit of 81% reduction in risk of progression or death vs placebo. This is an important outcome for Starr, who frequently treats patients with lung carcinoids.¹

TRANSCRIPTION

0:10 | When you talk about extrapancreatic NETs, that's a bigger…swath of patients. I should mention they included grade 1 to grade 3 in both groups. These are patients, essentially with NETs that arose in the small bowel most commonly, but 20% of patients had lung neuroendocrine tumors, which the terminology gets confusing, because they still call those carcinoids—so lung carcinoids; that was really interesting. Lung carcinoids are typically a bit of an orphan disease. We have 1 FDA-approved therapy for that. So that was really exciting as well.

0:47 | The other thing is that the PFS was favorable as compared to placebo, around 8 months or so. So certainly a positive study. These were all statistically significant. For small bowel neuroendocrine tumors, as I mentioned, sunitinib was approved for pancreas, so now we have an FDA-approved therapy for the majority of these patients we see with small bowel NETs in which we did not have a tyrosine kinase inhibitor. So I think that was really exciting. Also, the lung group, which is going to be reported a little bit more in detail at NANETS coming up. So stay tuned, but I'm excited to see that data, because I see a lot of patients with lung carcinoids.

_REFERENCE

_{1. Wolin EM, Zemla T, Geyer S, et al. Efficacy and safety of cabozantinib (CABO) for advanced lung and thymic neuroendocrine tumors (NET) after progression on prior therapy: Subgroup analysis of phase III CABINET Trial (Alliance A021602). Poster presented at: ESMO Congress 2025; Berlin, Germany; October 17-21, 2025. Poster 1712P.}