Cabometyx: A New Hope for Neuroendocrine Tumor Patients

Ipsen Korea’s Cabometyx (cabozantinib) has emerged as a potential treatment option for neuroendocrine tumor (NET) patients, particularly those with recurrent or metastatic disease who are ineligible for peptide receptor radionuclide therapy (PRRT).

NETs are rare tumors arising from hormone-producing neuroendocrine cells, with an incidence of approximately 1.5 cases per 100,000 people. These tumors commonly occur in the digestive tract, lungs, and pancreas. Despite their slow growth and relatively high survival rates, the disease’s rarity and limited treatment options pose significant challenges, especially for drug-resistant cases.

HitNews interviewed Dr. Jinwon Kim, a hematology-oncology specialist at Bundang Seoul National University Hospital, to gain insights into the overall characteristics of NETs and the latest advancements in treatment approaches.

“Compared to more common cancers like gastric or colorectal cancer, NETs are relatively rare, but they are not so uncommon as to be unseen in everyday medical practice. Neuroendocrine cells are distributed throughout the entire body, so more than 50% of NETs occur in the gastrointestinal tract. They are also commonly found in the lungs, pancreas, and digestive organs such as the intestines and rectum.

In some cases, the tumor itself secretes hormones, leading to symptoms like diarrhea or vomiting. However, in most cases, the condition is asymptomatic and is often discovered incidentally during imaging tests such as endoscopy or ultrasound.”

“For some patients, the cause can be attributed to a genetic factor known as Multiple Endocrine Neoplasia (MEN). However, this accounts for only a very small subset of patients. Aside from these cases, the exact cause of the disease remains unidentified.”

“NETs take a long time to diagnose because the tumors do not grow rapidly. While other cancers can double or triple in size within a year, NET tumors grow much more slowly. When a tumor is first detected through endoscopy, it is often monitored for a year. If the tumor grows during that time, surgery is performed.

A complete cure for cancer is typically determined when the tumor is removed through surgery or when it stops growing without treatment. However, in the case of NET, the disease may not progress for up to a year and a half, even without treatment. This is why the treatment duration is often considered long.

Nonetheless, slow-growing tumors still require attention because some patients are diagnosed in metastatic stages. For instance, there are patients with rectal NETs who undergo long-term monitoring because the tumor size does not increase. However, in some cases, the rectal tumor metastasizes to the liver, necessitating drug treatment. Since NET metastases can lead to fatal outcomes, it is crucial to monitor these tumors closely.”

“If surgery is possible when the tumor is first detected, it is performed immediately. For patients with metastases where surgery is not feasible, treatment is conducted with medication. NETs have unique markers, and targeted therapies that suppress these markers are used to prevent cancer progression. The goal of treatment is to inhibit further metastasis.

Unlike other cancers, NETs have a high survival rate even without treatment. However, using medication significantly slows disease progression, typically requiring about three years of treatment. NETs often express a high level of somatostatin receptors, and somatostatin analogs bind to these receptors to suppress tumor growth and hormone secretion.

The most commonly used agent is lanreotide. In the ‘CLARINET’ study, patients not treated with lanreotide experienced tumor growth to a certain extent within about 18 months, whereas those treated had a median progression-free survival (mPFS) of 32.8 months. Additionally, while conventional chemotherapy often causes severe side effects, lanreotide has relatively mild adverse effects.

Patients receive a monthly injection. Although some report pain at the injection site, there are no significant concerns about side effects aside from the need for regular injections.”

“Recently, new tyrosine kinase inhibitors (TKIs), like Cabometyx, have been introduced, and combinations of TKIs with angiogenesis inhibitors like bevacizumab are also being used.

Additionally, there is PRRT (Peptide Receptor Radionuclide Therapy), a treatment that targets the somatostatin receptors highly expressed in NETs. Using receptor expression as a guide, CT imaging and ‘DOTATOC PET’ attach radiolabeled substances to these receptors, causing NET tumors to emit light.

PRRT goes beyond diagnosis by incorporating therapeutic radioisotopes, enabling radiation therapy to target only NET tumors. While it is expensive, it is covered by health insurance. However, PRRT is not suitable for all patients and has a limited number of treatment sessions. In such cases, drugs like Cabometyx become viable options.

Although Cabometyx is not yet approved for use in South Korea, it offers a new treatment option for patients who have developed resistance to existing drugs or have no other available treatments. It could be particularly effective for patients who relapse after achieving remission of localized disease or for the approximately 20% of patients diagnosed with metastatic disease from the start.”

“Although the treatment environment has improved, the disease often eventually recurs or progresses. PRRT, for instance, does not aim to achieve a complete cure but rather to shrink the tumor and maintain its condition. The biggest challenge arises when the disease progresses again, leaving patients without effective treatment options.

Subcutaneous injections like lanreotide can cause discomfort at the injection site, and the need for long-term treatment over two to three years places a significant burden on patients. Tyrosine kinase inhibitors (TKIs), while effective, often have more severe side effects compared to lanreotide, which can also be a major source of difficulty for patients.”

A: “Many patients are unfamiliar with NET and may question whether treatment is necessary since the tumors often grow slowly. However, as there are cases where this disease leads to fatalities, it is crucial to pay closer attention and undergo regular check-ups. Routine endoscopy or ultrasound can help detect the condition early.

While diagnosis was previously challenging due to unclear criteria, increased awareness and the establishment of diagnostic standards now allow for quicker detection and prompt treatment. With many new medications emerging, patients should remain hopeful about ongoing treatment options.

NET is a condition that can be actively managed. Although it is rare, the number of patients is steadily increasing, and drug treatments can significantly extend progression-free survival (PFS). In the past, these treatments were not covered by insurance, but today, effective drugs are available with insurance support, improving survival rates. Therefore, it is important to stay vigilant, continue regular follow-ups, and monitor the tumor closely if detected.”