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Neuroendocrine ๐Ÿ’Š Treating the cancer

The CABINET trial: cabozantinib for advanced neuroendocrine tumors

For advanced neuroendocrine tumors that had kept growing despite other treatments, the pill cabozantinib — which cuts off a tumor’s blood supply — more than doubled the time the cancer was held in check, in both pancreatic and non-pancreatic types.

~9 min readPhase IIINEJM2025

Who is this for?

This is for people with advanced neuroendocrine tumors (NETs) that have continued to grow despite earlier treatments.

The trial studied two separate groups, because NETs behave differently depending on where they start:

  • Extrapancreatic NETs — those arising outside the pancreas, most often in the gut (stomach, intestine) or lungs.
  • Pancreatic NETs — those arising in the pancreas.

Everyone in the trial had already tried the usual options — and their cancer had progressed — so they needed a new approach.

The key terms, in plain language Neuroendocrine tumors (NETs) are an uncommon group of cancers that grow from hormone-producing cells scattered through the body (gut, lungs, pancreas). They are often slow-growing, but when advanced they are not curable. Cabozantinib is a once-daily pill — a “tyrosine kinase inhibitor” — that mainly works by blocking the growth of new blood vessels the tumor needs (an anti-angiogenic effect). Progression-free survival is how long the cancer is held in check before it grows again.

What kind of trial is this?

CABINET was a phase III randomized, placebo-controlled trial — the most rigorous kind. Notably, it was run by an academic cooperative group funded by the US National Cancer Institute, not by a drug company — the kind of publicly-funded study that answers important questions for less common cancers.

Understanding the disease
Finding cancer earlier
Preventing recurrence
Treating the cancer
Feeling better during treatment
First steps in humans
How we make decisions

Background: running low on options

Neuroendocrine tumors are uncommon and often grow slowly, but once they have spread they can’t be cured, and treatment is about controlling them for as long as possible. There are several tools — hormone-calming injections (somatostatin analogues), a targeted radioactive treatment (a form of “theranostics” called Lu-177 dotatate), and pills such as everolimus or sunitinib — but one by one these tend to stop working, and options run short.

Cabozantinib works differently: it chokes off the new blood vessels that tumors build to feed themselves, and blocks several other growth signals. It had shown promise in an earlier, smaller study, so CABINET put it to a rigorous test in people whose NETs had already progressed through other treatments.

Time the cancer was held in check: cabozantinib vs placebo Bar chart of median progression-free survival. Neuroendocrine tumors outside the pancreas: 8.4 months with cabozantinib versus 3.9 months with placebo. Pancreatic neuroendocrine tumors: 13.8 months with cabozantinib versus 4.4 months with placebo. Cabozantinib Placebo NETs outside the pancreas Cabo 8.4 mo Placebo 3.9 mo Pancreatic NETs Cabo 13.8 mo Placebo 4.4 mo 0 5 10 15 months
Median time the cancer was held in check before growing again. In both types of neuroendocrine tumor, cabozantinib roughly doubled to tripled that time compared with placebo.

The trial: what was tested and how

CABINET enrolled 298 people across the two groups (203 with extrapancreatic NETs, 95 with pancreatic NETs). Within each group, people were randomly assigned (2 to 1) to receive either cabozantinib (a 60 mg pill once daily) or a placebo. People on placebo whose cancer grew were allowed to cross over and receive cabozantinib.

The main measure was progression-free survival — how long the cancer was held in check. The benefit was so clear that an independent monitoring board recommended stopping the trial early.

Results: what they found

In both groups, cabozantinib substantially delayed the cancer’s growth.

Cabozantinib vs placebo — time the cancer was held in check

Pancreatic neuroendocrine tumors
13.8 moCabozantinib vs 4.4 moPlacebo

The cancer was held in check about three times longer — a 77% lower risk of progression or death (HR 0.23).

Neuroendocrine tumors outside the pancreas
8.4 moCabozantinib vs 3.9 moPlacebo

More than double the time before the cancer grew — a 62% lower risk of progression or death (HR 0.38).

The trade-off: side effects
~63%Cabozantinib, grade 3+ vs ~25%Placebo

Serious side effects were more common with cabozantinib — chiefly high blood pressure, fatigue, and diarrhea — and many people needed a lower dose. This is a real trade-off to weigh against the benefit.

What are neuroendocrine tumors?

They grow from “neuroendocrine” cells — hormone-making cells found throughout the body, especially in the gut, lungs, and pancreas. Some produce hormones that cause symptoms (flushing, diarrhea); many don’t. They are usually slower-growing than common cancers, which is why treatment often focuses on controlling them over long periods rather than an all-out attack.

How does cabozantinib work?

Tumors have to build their own blood supply to keep growing. Cabozantinib blocks the signals (chiefly VEGF) that let them do this, essentially starving the tumor of new blood vessels; it also blocks several other growth pathways. That is a different strategy from hormone injections, radioactive treatments, or chemotherapy — which is why it can help after those have stopped working.

Did it shrink tumors, or help people live longer?

Cabozantinib mostly halts growth rather than shrinking tumors — outright shrinkage was uncommon (about 5% of extrapancreatic and 19% of pancreatic NETs), while most people’s cancer simply stopped growing for a while. Overall survival was not clearly improved, but that is hard to judge here: many people on placebo crossed over to cabozantinib once their cancer grew, which tends to blur any survival difference. The clear, measured benefit is longer control of the disease.

Look up this trial CABINET · Cabozantinib vs placebo in advanced neuroendocrine tumors · NCT03375320
View on ClinicalTrials.gov →

The bottom line

For advanced neuroendocrine tumors that have progressed through other treatments, the pill cabozantinib meaningfully extended the time the cancer was held in check — roughly tripling it in pancreatic NETs (13.8 vs 4.4 months) and more than doubling it in NETs elsewhere (8.4 vs 3.9 months). It mostly halts growth rather than shrinking tumors, and it comes with real side effects to manage, but for a group of patients with few remaining options, it adds a valuable new one.

What this could mean for you

  • A new option after others stop working. If a neuroendocrine tumor has progressed through hormone injections, radioactive treatment, or other pills, cabozantinib may be worth discussing.
  • It works differently. By cutting off the tumor’s blood supply, it can help even when previous treatments no longer do.
  • Side effects are real. High blood pressure, fatigue, and diarrhea are common; doses are often adjusted, and monitoring is part of the plan.
  • It controls, it doesn’t cure. The goal is to hold the cancer steady for longer, which for slow-growing NETs can be genuinely worthwhile.
For information purposes only. This summary explains published research in plain language. It is not medical advice and is not a substitute for care from your own doctors. Trial results describe what happened in a study group and may not apply to your situation. Always discuss your diagnosis, treatment options, and any clinical trial with your own oncology team before making any decisions.

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