Recent Advances in Medical Therapy for Urological Cancers

Abstract

The mainstay of medical treatment has been tyrosine kinase inhibitors (TKIs) for renal cell cancer (RCC), cytotoxic chemotherapy for urothelial cancer (UC), and androgen deprivation therapy for prostate cancer. These therapeutic modalities still play important roles in these malignancies. However, immune checkpoint inhibitors (ICIs) that target PD-1/PD-L1 or CTLA-4 are being rapidly introduced for the treatment of metastatic urological cancers, just as they have been for other malignancies. Currently, the paradigm of medical treatment for patients with metastatic urological cancer is dramatically changing. Accordingly, we need to organize and summarize the new therapeutic tools, which include immune checkpoint inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, and antibody-drug conjugates (ADCs). This review provides an overview of agents and regimens that have just launched or will be launched in the near future in Japan. Based on the promising anti-tumor efficacy and manageable safety profiles being demonstrated in clinical trials, these new agents and therapies are expected to be rapidly introduced in Japanese clinical practice. Additionally, the newly designed ADC, enfortumab vedotin, which comprises a fully human monoclonal antibody conjugated to an anti-cancerous agent via a protease-cleavable linker, has just been launched in Japan. In order to provide the optimal treatment for our patients, we need to completely understand these new therapeutic tools.

Keywords: PARP inhibitor; androgen receptor axis targeted agent; antibody-drug conjugate; enfortumab vedotin; immune checkpoint inhibitor; olaparib.

Figure 1

Schematic of standard of care in 2022 for medical treatment of metastatic urological cancers, including renal cell cancer (mRCC, A), urothelial cancer (mUC, B), and hormone naïve prostate cancer (mHNPC, C). Abbreviations: CR: complete response; PR: partial response, SD: stable disease; mBRCA(-): BRCA1/2 mutation negative; mBRCA(+): BRCA1/2 mutation positive; Caba: cabazitaxel; Abi: abiraterone acetate; Enz: enzalutamide; MSI-high: microsatellite instability-high. *When docetaxel is administered as the first-line therapy for metastatic hormone-sensitive prostate cancer (HSPC), abiraterone acetate, enzalutamide, cabazitaxel, Ra-223, pembrolizumab (MSI-high), and olaparib (mBRCA[+]) are the candidates for metastatic castration-resistant prostate cancer (CRPC).