Immunotherapy has been an area of significant research in recent years. A plethora of clinical trials have been undertaken investigating their use in the treatment of metastatic bladder cancer. Immune checkpoint inhibitors have emerged as new targeted agents (e.g. pembrolizumab, avelumab, nivolumab) that are used in certain settings. They could also be considered in patients with a poor functional baseline instead of chemotherapy, but is still an unclear area requiring further research.
Pembrolizumab (pharmaceutical name Keytruda) does not have a survival benefit over standard chemotherapy. As such, it is approved by the TGA as the next-line option in patients who are not eligible for any platinum-based chemotherapy. However, it is not PBS subsidised for this purpose. Furthermore, pembrolizumab is also used as second-line treatment in patients who have had metastatic bladder cancer after having had platinum-based chemotherapy. It is both TGA and PBS-approved for this indication.
Similarly, atezolizumab (pharmaceutical name Tecentriq) is also TGA-approved in patients unable to have cisplatin and whose tumors express a protein called programmed death-ligand 1 (PD-L1). However, like pembrolizumab, it is also not PBS subsidised, which limits uptake of these agents in Australia.
Avelumab (pharmaceutical name Bavencio), another checkpoint inhibitor, is the recommended maintenance therapy for patients who have responded to the first-line platinum-based chemotherapy in Australia.
Nivolumab (pharmaceutical name Opdivo), a PD-1 inhibitor, is another second-line therapy option after chemotherapy in patients with metastatic bladder cancer. It is TGA-approved, but not PBS-subsidised in Australia.
Currently, a new antibody-drug conjugate called Enfortumab vedotin (EV) is used as third-line treatment on patients who have progressed both on chemotherapy and immunotherapy. A large clinical trial (EV302) comparing EV combined with immunotherapy against chemotherapy is underway with the results eagerly awaited.
Targeted molecular therapy of patient genomics is another area of exciting growth in coming years. There are also other clinical trials ongoing currently involving either single or multi-agents in a constantly shifting landscape.
Shane Quin is a Urology Research Fellow at Austin Health and Secretary for BladderCancer.org.au