29 January 2020

Will PSMA-targeting diagnostics and therapeutics revolutionize Prostate Cancer care?

Prostate cancer (PC) is the fourth most common cancer worldwide, affecting approximately 1.3 million people, with approximately 1 in 9 men being diagnosed during their lifetime. Patients with localized disease typically respond well to surgery. Should the disease recur, patients are often treated with androgen deprivation therapy. While such therapy has been around for a long time, newer antiandrogen therapies have more recently become available: Pfizer’s Xtandi, JNJ’s Erleada and Zytiga, and Bayer’s Nubeqa for patients with castrate-sensitive (CSPC) as well as for castrate-resistant (CRPC) disease. These therapies regularly result in durable responses from PC patients, but what happens after these newer options fail?

Targeted therapies compete for approval in CRPC

Patients with CRPC that is metastatic, eventually develop resistance to newer androgen deprivation treatments, leaving patients with few effective therapeutic options. However, the tide may be turning soon, with promising therapies in development including PARP inhibitors, AKT inhibitors, anti-PD-L1 checkpoint inhibitors, and prostate specific membrane antigen (PSMA)-targeted radioligands.

In 2020, AstraZeneca’s Lynparza and Clovis’ Rubraca are expected to be FDA-approved in metastatic CRPC, having been granted expedited reviews due to the regulator’s acknowledgement of the large unmet need in this setting. Roche is hoping that its AKT inhibitor, ipatasertib, will follow, with approval anticipated in 2021. Leading checkpoint inhibitors from Merck (Keytruda), BMS (Opdivo), and Roche (Tecentriq) are also being positioned in the metastatic CRPC setting, with data for the latter expected this year.

But, perhaps most exciting of all the emerging targeted therapies has been Endocyte’s Lutetium-177 PSMA-617, with early data showing compelling efficacy in patients with CRPC, regardless of PSMA expression levels. The promise of targeting PSMA with this radioligand has not been lost on Novartis, which acquired Endocyte and another leading developer of Lutetium-177 PSMA-targeting agents, Advanced Accelerator Applications, in 2018. With physician’s reporting that patients are flying across the world to access this therapy ahead of the more toxic chemotherapies available, data from Novartis/Endocyte’s phase 3 trial, which is due to reach primary completion in Summer 2020, is eagerly anticipated.

Targeting PSMA could also revolutionize PC diagnostic imaging

The potential of targeting PSMA does not end there. While molecular imaging has long been used to enhance the accuracy of PC diagnosis and improve patient outcome, the development of PSMA-targeted radiotracers has the potential to take things to a whole new level. The use of PSMA-PET/CT scanning is becoming more and more common, particularly in Australia and continental Europe, where its use is supported by the European Association of Urology guidelines, due to its ability to detect small volume disease in patients expressing low serum PSA. This imaging modality could help support decisions on the need for surgery, or facilitate earlier treatment of recurrent disease, something that resonates with patients, physicians, and payers.

With recent evidence published in the Lancet suggesting that PSMA-PET/CT imaging is superior to conventional fluciclovine-18 based imaging, it seems to be only a matter of time before PSMA-based imaging is adopted more widely as standard imaging practice in PC.