Selpercatinib on the PBS

Selpercatinib has been added to the Pharmaceutical Benefits Scheme (PBS) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). This is a targeted therapy for patients with RET (rearranged during transfection) fusion-positive disease.

While NSCLC is the most common type of lung cancer, RET fusions are only found in 1-2% of cases. Data suggests that RET fusions may be more likely to occur in patients who are female, younger than 60 years, non-smokers, or of Asian background.

Selpercatinib is a highly selective inhibitor of the RET receptor tyrosine kinase. Under normal conditions, RET plays an important role in the development of a variety of tissues. However, genetic alterations are associated with uncontrolled cellular proliferation and the development of cancer.

A recent randomised clinical trial compared the efficacy of selpercatinib with platinum-based chemotherapy (with or without pembrolizumab) in advanced RET fusion-positive NSCLC. Median progression-free survival was 24.8 months for selpercatinib (95% CI: 16.9 to not estimable) and 11.2 months for control (95% CI: 8.8 to 16.8).

Selpercatinib is usually administered twice daily without regard to food. However, patients who are also taking a proton pump inhibitor should take their selpercatinib dose with food. Metabolism is primarily via CYP3A4. Selpercatinib dose reduction may be required if co-administered with a strong CYP3A4 inhibitor (e.g. itraconazole, voriconazole, ritonavir, saquinavir, posaconazole). The concomitant use of strong inducers of CYP3A4 (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin, St. John’s Wort) is not recommended.