Cabozantinib

Cabozantinib is an innovative drug being studied in various clinical trials for its potential to treat multiple types of cancer. This article explores the ongoing research into cabozantinib’s effectiveness and safety across different cancer types, including renal cell carcinoma, prostate cancer, and other solid tumors. We’ll examine the key findings from recent clinical trials and what they mean for patients and the future of cancer treatment.

Table of Contents

What is Cabozantinib?

Cabozantinib is a medication used to treat various types of cancer. It’s also known by several other names, including XL184, Cometriq, Cabometyx, and BMS907351[1]. This drug is part of a class of medications called tyrosine kinase inhibitors, which work by targeting specific proteins in cancer cells to slow down or stop their growth[2].

How Does Cabozantinib Work?

Cabozantinib works by inhibiting several proteins that are involved in cancer growth and spread. Specifically, it targets proteins called RET, ROS1, NTRK, MET, and AXL[2]. By blocking these proteins, cabozantinib can:

  • Slow down or stop cancer cell growth
  • Prevent the formation of new blood vessels that feed tumors (a process called angiogenesis)
  • Reduce the spread of cancer to other parts of the body (metastasis)

Conditions Treated with Cabozantinib

Cabozantinib has been studied and used to treat several types of cancer, including:

  • Advanced or metastatic renal cell carcinoma (kidney cancer)[3]
  • Non-small cell lung cancer, especially in patients with specific genetic changes like RET, ROS1, or NTRK fusions[2]
  • Medullary thyroid cancer[2]
  • Advanced or metastatic cervical cancer[4]
  • Pancreatic cancer[5]
  • Multiple myeloma (a type of blood cancer)[6]
  • Meningioma (a type of brain tumor)[1]
  • Plexiform neurofibromas in patients with neurofibromatosis type 1 (NF1)[7]

How is Cabozantinib Administered?

Cabozantinib is typically taken orally (by mouth) in the form of tablets or capsules. The dosage and schedule can vary depending on the specific condition being treated and the patient’s individual needs. Some common dosing regimens include:

  • 60 mg once daily[4]
  • 40 mg once daily, with potential escalation to 60 mg based on tolerability[7]
  • Dosing based on body surface area for children (e.g., 30 mg/m2/day)[7]

Treatment cycles are often 28 days long, and patients may continue taking cabozantinib as long as they are benefiting from it and not experiencing severe side effects[4].

Ongoing Clinical Trials

Cabozantinib is currently being studied in various clinical trials to determine its effectiveness in treating different types of cancer and to explore new combinations with other treatments. Some ongoing studies include:

  • Combining cabozantinib with immunotherapy drugs for kidney cancer[3]
  • Using cabozantinib in combination with chemotherapy drugs like gemcitabine for pancreatic cancer[5]
  • Evaluating cabozantinib’s effectiveness in treating plexiform neurofibromas in children and adults with NF1[7]

Potential Side Effects

Like all medications, cabozantinib can cause side effects. Common side effects may include:

  • Fatigue
  • Diarrhea
  • Nausea
  • Decreased appetite
  • Hand-foot syndrome (redness, swelling, and pain on the palms of hands and soles of feet)
  • High blood pressure

More serious side effects, though less common, can include:

  • Bleeding problems
  • Wound healing complications
  • Liver problems
  • Blood clots

Patients taking cabozantinib are closely monitored by their healthcare team for any side effects, and the dose may be adjusted if necessary[7].

Aspect Details
Main Cancer Types Studied Renal Cell Carcinoma, Prostate Cancer, Non-Small Cell Lung Cancer, Urothelial Carcinoma
Common Dosages 20 mg, 40 mg, 60 mg daily
Administration Oral tablets, taken once daily
Primary Outcome Measures Progression-Free Survival, Objective Response Rate, Maximum Tolerated Dose
Secondary Outcome Measures Overall Survival, Duration of Response, Safety and Tolerability
Combination Therapies Often studied in combination with immunotherapy drugs (e.g., atezolizumab)
Trial Phases Phase 1, Phase 2, and Phase 3 studies ongoing
Patient Populations Both treatment-naive and previously treated patients, depending on the study
Safety Monitoring Regular assessment of adverse events, using criteria such as CTCAE v4.0 or v5.0
Biomarker Studies Some trials include analysis of biomarkers to predict or monitor treatment response

Ongoing Clinical Trials on Cabozantinib

  • Study of Cabozantinib for Patients with Advanced Renal Cell Carcinoma Previously Treated with One Immunotherapy Drug

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Italy
  • Study of Cabozantinib for Patients with Advanced Renal Cell Carcinoma After Checkpoint Inhibitor Treatment

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany
  • Study of Cabozantinib in Adults with Advanced Low-Grade Neuroendocrine Tumors

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Austria Germany
  • Study on the Safety and Effects of Temferon for Patients with Metastatic Renal Cell Carcinoma Using a Drug Combination

    Not recruiting

    1 1 1
    Italy
  • Study of Dabrafenib and Drug Combination for Patients with Metastatic Non-Clear Cell Kidney Cancer

    Not recruiting

    1 1 1
    Denmark
  • Study on Atezolizumab and Cabozantinib for Patients with Advanced Renal Cell Carcinoma After Tumor Progression Post-Immune Checkpoint Inhibitor Treatment

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany Poland
  • Study on Cabozantinib for Patients with Advanced Radioactive-Iodine Refractory Differentiated Thyroid Cancer

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Spain
  • Study of Belzutifan with Lenvatinib versus Cabozantinib in Adults with Advanced Renal Cell Carcinoma Who Have Previously Received Anti-PD-1/L1 Treatment

    Not recruiting

    1 1 1 1
    Austria Belgium Czechia Finland France Germany +7
  • Study Comparing Nivolumab and Cabozantinib with Sunitinib for Patients with Untreated Advanced Kidney Cancer

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Czechia Germany Greece Italy Poland Romania +1
  • Study Comparing Selpercatinib, Cabozantinib, and Vandetanib for Patients with Advanced RET-Mutant Medullary Thyroid Cancer

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Belgium Czechia France Germany Greece Italy +3

Glossary

  • Renal Cell Carcinoma (RCC): A type of kidney cancer that starts in the lining of small tubes in the kidney. It is one of the main cancer types being studied in cabozantinib trials.
  • Castration-Resistant Prostate Cancer (CRPC): A form of prostate cancer that continues to grow even when the amount of testosterone in the body is reduced to very low levels. Cabozantinib is being tested as a potential treatment for this advanced form of prostate cancer.
  • Progression-Free Survival (PFS): The length of time during and after treatment that a patient lives with cancer without it getting worse. This is a common measure used in cancer clinical trials to assess the effectiveness of a treatment.
  • Objective Response Rate (ORR): The proportion of patients whose cancer shrinks or disappears after treatment. This is often used as a measure of how well a cancer treatment is working in clinical trials.
  • Maximum Tolerated Dose (MTD): The highest dose of a drug that does not cause unacceptable side effects. Determining the MTD is often an important goal in early-phase clinical trials.
  • RECIST 1.1: Response Evaluation Criteria in Solid Tumors version 1.1. This is a standard set of rules used to measure how well a cancer patient responds to treatment in clinical trials.
  • Adverse Events (AEs): Any unfavorable and unintended sign, symptom, or disease temporarily associated with the use of a medical treatment or procedure. Monitoring AEs is crucial for assessing the safety of new treatments in clinical trials.
  • Biomarker: A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. Biomarkers are often used in clinical trials to help predict or monitor treatment response.
  • Immunotherapy: A type of cancer treatment that boosts the body's natural defenses to fight cancer. Some cabozantinib trials are exploring its use in combination with immunotherapy drugs.
  • Tyrosine Kinase Inhibitor (TKI): A type of targeted therapy that blocks specific enzymes called tyrosine kinases, which are involved in cancer cell growth and survival. Cabozantinib is a type of tyrosine kinase inhibitor.

References

  1. https://clinicaltrials.gov/study/NCT05425004
  2. https://clinicaltrials.gov/study/NCT01639508
  3. https://clinicaltrials.gov/study/NCT03463681
  4. https://clinicaltrials.gov/study/NCT04205799
  5. https://clinicaltrials.gov/study/NCT01663272
  6. https://clinicaltrials.gov/study/NCT01866293
  7. https://clinicaltrials.gov/study/NCT02101736