Oncology Overview: Cabozantinib for RCC, HCC

Cabozantinib (Cabometyx, Exelixis) is a kinase inhibitor approved for indications such as advanced renal cell carcinoma and hepatocellular carcinoma.

Cabozantinib (Cabometyx, Exelixis) is a kinase inhibitor approved for multiple indications. It is used for patients with advanced renal cell carcinoma, (RCC) and in combination with nivolumab (Opdivo) for patients with RCC. It is also indicated for patients with hepatocellular carcinoma (HCC) who have been treated with other medications, such as sorafenib. ¹

There are an estimated 76,000 new cases of RCC in the United States and approximately 14,000 deaths from it each year. ² The incidence for HCC is approximately 9.5 per 100,000 people in the United States and much higher percentage of it in Medicare, as well as among veteran patients.³

Cabozantinib comes in 20 mg, 40 mg, and 60 mg yellow tablet dosage forms. When it comes to the dosing for cabozantinib, the recommended dose is 60 mg by mouth, once daily, and 40 mg by mouth once daily, when taken with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks. It should be administered at least 1 hour before eating or 2 hours after. It is especially important for pharmacists to recognize not to substitute cabozantinib tablets with cabozantinib capsules. ¹

Cabozantinib inhibits the tyrosine kinase activity of MET, VEGFR-1, 2 and 3, and few other receptors. These receptors are involved in normal cellular function, as well as pathologic processes that may include oncogenesis, metastasis and drug resistance. Therefore, by inhibiting these receptors, cabozantinib blocks these activities in the body. ¹

Adverse events (AEs) seen from this drug in physician practices and in clinical trials include diarrhea, fatigue, decreased appetite, nausea, hypertension, vomiting, weight decrease, and constipation. When cabozantinib is used with nivolumab, there are other AEs also expected, such as dysgeusia, musculoskeletal pain, abdominal pain, cough and upper respiratory tract infections.

There are some precautions that should be taken when the patient is taking cabozantinib. These include hemorrhage or history of hemorrhage, perforations or fistulas, especially Grade 4 fistulas. If the patient experiences myocardial infarction or severe venous or arterial thromboembolic events, the drug should be discontinued.¹

Blood pressure should be monitored for these patients with cardiac background and taking cabozantinib. As mentioned in the AEs, this drug may cause severe diarrhea. If so, the provider should be notified and to stop cabozantinib immediately until the AE resolves.

Cabozantinib can also elevate hepatic enzymes, such as ALT or AST, and they should be monitored before initiation of the drug. Also, if the patient has any type of nephrotic event, the dose should be discontinued until the event is resolved. Cabozantinib should be stopped before any major surgery, at least 2 to 3 weeks before since it may impair the wound healing process.

In interactions, when strong CYP3A4 inhibitors are used, the dose for cabozantinib is to be reduced, because it may increase levels of the drug in the body to toxic levels. Conversely, if a strong CYP3A4 inducer drug is used with cabozantinib, the dose for cabozantinib should be increased because these inducers will metabolize cabozantinib faster in the body.

The safety and efficacy data for cabozantinib come from various data. In randomized, active-controlled trials, 409 patients with RCC were enrolled as well as 467 patients with HCC diagnosis. The RCC trials were CABOSUN and METEOR, and the HCC study was CELESTIAL. Another study evaluated the use of cabozantinib and nivolumab 240 mg/m2 every 2 weeks, which included 320 patients with RCC and in the active-controlled trial called CHECKMATE.¹

The safety of cabozantinib was studied in the METEOR study, in which 331 patients received cabozantinib 60 mg once daily and 322 patients received everolimus 10 mg once daily until disease progression or unacceptable toxicity.

The median duration of the study treatment was approximately 7.6 months in the cabozantinib arm and 4.4 months in the everolimus arm. The mentioned AEs in this article were seen in these clinical trials, which included vomiting, weight loss, and constipation. The most frequent AEs were fatigue, hypertension and diarrhea.

In these studies, the dose for cabozantinib was reduced in 60% of the patients and 24% for patients receiving everolimus. Twenty percent of the patients received cabozantinib 20 mg once daily per day.

In the CABOSUN study, which was a randomized, open label trial, the safety of the cabozantinib was studied in patients with RCC, with 78 of patients receiving cabozantinib 60 mg once daily and 72 patients received sunitinib 50 mg once daily. These dosages were given in increments of 4 weeks on and 2 weeks off, and until the patients had unacceptable toxicity.

The median duration of the treatment was apporximately 6.5 months. In this study, within 30 days of the treatment, there were 4 deaths in patients treated with cabozantinib and 6 deaths in patients treated with sunitinib. Two of the patients died because of gastrointestinal perforations, 1 of the patients died because of acute renal failure, and 1 patient due to the clinical deteriorations.¹

Cabozantinib is a new drug that should be prescribed to the appropriate patients with RCC or HCC diagnosis who qualify for the medications. Patients should be given the patient education material about the drug and to learn the considerations of treatment. Patients should be reminded to swallow the medication, take it at the same time every day, and 1 hour before or 2 hours after meals.

Cabozantinib should not be crushed and patients should not consume grapefruit juice or other types of juice. These patients should be reminded about the AEs that cabozantinib can cause and to recommend the patients to report any of the AEs that may happen during the course of treatment with this drug.

References

  1. CABOMETYXUSPI.pdf
  2. Epidemiology, pathology, and pathogenesis of renal cell carcinoma - UpToDate
  3. Epidemiologic, humanistic and economic burden of hepatocellular carcinoma in the USA: a systematic literature review | Hepatic Oncology (futuremedicine.com)