Expanded PBS Listing for Cabozantinib

The Pharmaceutical Benefits Scheme (PBS) listing for cabozantinib has been expanded to include non-clear cell renal cell carcinoma (RCC). Cabozantinib is now PBS subsidised for stage IV RCC (clear cell and non-clear cell) in addition to locally advanced or metastatic differentiated thyroid cancer. Cabozantinib is also indicated for the treatment of hepatocellular carcinoma in adults previously treated with sorafenib. However, this is currently not a PBS-subsidised indication.

Non-clear cell RCC is a less common subtype of RCC, accounting for around 20% of cases. Expansion of the PBS listing to include non-clear cell subtypes is significant as there were previously no targeted therapies available on the PBS for this subset of patients. While evidence is limited in this group, the clinical benefit of cabozantinib appears to be similar to that seen in patients with clear cell RCC.

Cabozantinib inhibits multiple receptor tyrosine kinases associated with tumour growth, angiogenesis, drug resistance, and metastatic progression. The tablets should be swallowed whole and taken on an empty stomach. Common adverse effects include fatigue, diarrhoea, palmar-plantar erythrodysesthesia syndrome, and dry mouth. Fistulas have been reported in some studies, with persistent or recurrent diarrhoea noted as a potential risk factor. Patients should be advised to contact their doctor if they experience severe diarrhoea.

Cabozantinib is metabolised by cytochrome P450 3A4. Administration with strong inhibitors of this enzyme (e.g. ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice) may increase the risk of toxicity. Conversely, chronic combination with inducers (e.g. phenytoin, carbamazepine, rifampicin, phenobarbital, St. John’s Wort) may reduce efficacy.