The anti-cancer drug we introduced in this issue - cabozantinib (Cabozantinib, XL184). This is a multi-target small molecule tyrosine kinase inhibitor (TKI), whose targets include MET, VEGFR1/2/3, ROS1, RET, AXL, NTRK, KIT, etc.
As early as 2012, cabotinib was first approved for the treatment of progressive and metastatic medullary thyroid carcinoma. After that, within a few years, it added approved indications, including second-line treatment for advanced renal cell carcinoma with antiangiogenesis (2016), first-line treatment for advanced renal cells (2017), and second-line treatment for advanced liver cancer (2019). However, it has not yet been listed in mainland China.
Although cabotinib has been approved for indications in three cancer types, it has (or is currently in progress) clinical trials in many solid tumor such as non-small cell lung cancer , prostate cancer , urothelial cancer, etc., which has significantly benefited some tumor patients. Let's take a look at how effective it is.
Research results of some clinical trials conducted by
renal cell carcinoma
Phase III clinical trial METEOR compared the treatment effects of 60 mg cabotinib and 10 mg everolimus on patients with advanced renal cancer (70% of which are second-line treatments). The results showed that the disease control rate (DCR) of the cabotinib group was 83%, while that of the everolimus group was 66%. The subgroup analysis results showed that cabotinib can improve PFS, ORR and OS in patients with advanced renal cancer.
Phase II clinical trial CABOSUN compared 60mg of cabotinib with 50mg sunitinib . The former was only used as the first-line treatment for patients with moderate and low-risk risks. The results showed that the DCRs of cabotinib and sunitinib were 75% and 47%, respectively, and patients taking cabotinib had a significantly lower risk of progress.
Phase III clinical trial compared the efficacy of nivolumab (240mg/2 weeks) + cabotinib (40mg/day) or sunitinib (50mg/d) in adult patients with previously untreated advanced renal clear cell carcinoma. The results showed that the median progression-free survival in the nivolumab + cabotinib group was 16.6 months, while the sunitinib group was 8.3 months; by 12 months, the overall survival rate in the nivolumab + cabotinib group was 85.7%, while the sunitinib group was 75.6%.
hepatocellular carcinoma
A phase III clinical trial compared cabotinib and placebo patients with hepatocellular carcinoma who had received sorafenib and and had received up to two systemic treatments. The results showed that the median progression time in the cabotinib group was 5.4 months compared with 1.9 months in the placebo group; further analysis of patients receiving sorafenib as the only previous treatment showed that the median OS in the cabotinib group was 11.3 months, higher than the 7.2 months in the placebo group.
Radical iodine-refractory differentiated thyroid cancer
Phase III clinical trial CSOMIC-311 compared the treatment effects of cabotinib and placebo in patients with radioiodine-refractory differentiated thyroid cancer. The results showed that cabotinib significantly improved progression-free survival.
Urological carcinoma
Interim analysis of a single-arm phase II study of 16 patients with advanced urothelial carcinoma (those patients received cabotinib (40 mg/day) and durvalumab after receiving platinum-based chemotherapy, showed that 37.5% of patients had objective remission, and 4 of them still responded at 8 months.
Non-small cell lung cancer
A randomized controlled trial was performed on patients with non-small cell lung cancer who had not received erlotinib or MET TKI before using cabotinib (60mg/day), cabotinib (40mg/day) + erlotinib or erlotinib alone. The results showed that the progression-free survival of the cabotinib and cabotinib + erlotinib groups were significantly better than erlotinib alone; the overall survival of the cabotinib group was also significantly better than that of the erlotinib group.Two dosage forms of
cabotinib
FDA approved cabotinib is developed by Exelixis and Puyisheng Pharmaceuticals. It is divided into two dosage forms, one is capsule (trade name Cometriq) and the other is tablet (trade name Cabometyx), and both are oral drugs.
Applicable population
renal cell carcinoma (RCC):
- advanced renal cell carcinoma patients;
- combined with nivolumab is used for first-line treatment of patients with advanced renal cancer;
hepatocellular carcinoma (HCC):
html l8thyroid cancer :
- 9 was used for children and adults aged 12 years and older who had refractory locally advanced or metastatic differentiated thyroid carcinoma (DTC) who had progressed after VEGFR targeted therapy and were intolerant to radioactive iodine;
- progressive metastatic medullary thyroid carcinoma (MTC).
- When taking medicine alone : 60 mg each time, once a day, until the disease progresses or impermanent toxicity appears.
- When combined with nivolumab
Usage and dosage
Cabometyx (Tablet)
①Renal cell carcinoma
②Hepatocellular carcinoma
- 60mg each time, once a day, until the disease progresses or impermanent toxicity appears
③Different thyroid cancer
ht For children and adult patients aged 12 years and above who have a body surface area of ≥1.2m2, the recommended dose is 60 mg once a day until the disease progresses or intolerable toxicity occurs; for children and adult patients aged 12 years and above who have a body surface area of <1.2m2,>Cometriq (capsule)
- 140mg each time, once a day, taken on an empty stomach until the disease progresses or impermanent toxicity appears.
Note:
Please do not replace capsules with cabotinib tablets.
Adverse reactions
Cabometyx (tablet)
The most common adverse reactions (≥20%)
Medications alone: diarrhea, fatigue, nausea, loss of appetite, red and swelling of palms and feet (PPE), Hypertension , vomiting, weight loss and constipation, etc.
combined with nivolumab: diarrhea, fatigue, hepatotoxicity, red and swollen palms and feet tenderness syndrome (PPE), stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, loss of appetite, nausea, dyspepsia, abdominal pain, cough and upper respiratory tract infection , etc.
Cometriq (capsule)
The most common adverse reactions (≥25%)
Diarrhea, stomatitis, red and swollen palms and feet tenderness syndrome (PPE), weight loss, loss of appetite, nausea, fatigue, oral pain, hair color change, taste disorders, hypertension, abdominal pain and constipation.
The most common laboratory test results are abnormal (≥25%)
AST, ALTh, lymphocytes decreased, alkaline phosphatase increased, hypocalcemia , neutropenia, thrombocytopenia, hypophosphatemia and hyperbilirubinemia.
Precautions
Cabometyx (Tablet)
, bleeding
If you have a recent history of bleeding, please do not use Cabometyx.
monitoring symptoms. For grade 4 fistulas or perforations, stop using Cabometyx.
3, thrombosis
Myocardial infarction or severe venous or arterial thromboembolism events occur, and Cabometyx is stopped.
4, hypertension and hypertension crisis
regular monitoring of blood pressure . If hypertension treatment cannot fully control hypertension, Cabometyx should be suspended; if hypertension crisis or hypertension cannot be controlled, Cabometyx should be stopped.
5, diarrhea
can lead to severe diarrhea. Discontinue treatment when symptoms appear until the symptoms subside or reach level 1. Standard antidiarrhea therapy is recommended.
6, Palm and foot redness and tenderness syndrome (PPE)
Discontinue treatment when symptoms occur until the symptoms subside or reach level 1.
7, hepatotoxicity
, when used in combination with nivolumab, high-frequency 3/4 ALT and AST may occur. Regular monitoring of liver function before and during treatment, discontinue use of Cabometyx and/or nivolumab when severe or life-threatening hepatotoxicity occurs, and treat with corticosteroids.
8, adrenal insufficiency
and nivolumab may occur. When adrenal insufficiency occurs at grade 2 or above, symptomatic treatment will be initiated, including hormone replacement according to clinical indications. Discontinue Cabometyx and/or nivolumab depending on the severity of the condition.
9, proteinuria
Monitor urine protein . When it occurs, pause Cabometyx until proteinuria subsides.
0, jaw osteonecrosis (ONJ)
Disable Cabometyx at least 3 weeks before invasive dental surgery.
1, Wound healing
Use of Cabometyx for at least 3 weeks before elective surgery, and use of Cabometyx for at least 2 weeks after major surgery and closure healing. The safety of recovering Cabometyx after wound healing complications has not been determined.
2. Reversible posterior leukofolio syndrome (RPLS):
Stop using Cabometyx.
3, Thyroid dysfunction
Monitor thyroid function before and during treatment.
4, hypocalcemia
, pause, reduce the dose, or permanently discontinue Cabometyx according to the severity of the disease.
5, embryo-fetal toxicity
can cause damage to the fetus. Women are advised to pay attention to the potential risks to the fetus and take effective contraception measures.
Cometriq (capsule)
, perforation and fistula
Monitoring symptoms. For grade 4 fistulas or perforations, stop using Cometriq.
If you have a recent history of bleeding, please do not use Cometriq.
3, thrombosis
Myocardial infarction or severe venous or arterial thromboembolism events occur, and the use of Cometriq will be stopped.
4, Wound healing,
Use of Cabometyx for at least 3 weeks before elective surgery, and use Cometriq for at least 2 weeks after major surgery and closing healing, until the wound is completely healed. The safety of recovery of Cometriq after wound healing complications has not been determined.
5, hypertension and hypertension crisis
Regularly monitor blood pressure. If hypertension treatment cannot fully control hypertension, Cometriq should be suspended; if hypertension crisis or hypertension cannot be controlled, Cometriq should be stopped.
6, jaw osteonecrosis (ONJ)
Check the use of Cometriq at least 3 weeks before invasive dental surgery.
7, diarrhea
can lead to severe diarrhea. Discontinue treatment when symptoms appear until the symptoms subside or reach level 1. Standard antidiarrhea therapy is recommended.
8, Palm and foot redness and tenderness syndrome (PPE)
Discontinue treatment when symptoms occur until the symptoms subside or reach level 1.
9, proteinuria
monitors urine protein, and nephrotic syndrome patients are discontinued.
0, Reversible Posterior Leukofocal Syndrome (RPLS)
Reversible Posterior Leukofocal Syndrome (RPLS): Stop using Cometriq.
1, embryo-fetal toxicity
can cause damage to the fetus. Women are advised to pay attention to the potential risks to the fetus and take effective contraception measures.
****This article is original by Meizhong Jiahe. If you need to reprint, please contact authorization and indicate the source. ****
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