Professor Gillessen began by noting that theranostics entails treating the “right” patient by image selection. This requires an appropriate cell surface target, with corresponding ligands, linkers, and isotopes.


Based on these results, the European Medicines Agency (EMA) approved 177Lu-PSMA-617, together with ADT, in prostate cancer patients previously treated with androgen receptor pathway inhibitors and a previous taxane.
When considering the role of 177Lu-PSMA-617 in the treatment paradigm of mCRPC patients, it is critical to consider prior treatments received in the mHSPC disease space. Professor Gillessen proposed four treatment paradigms based on the initial treatment received:
1. ADT alone for mHSPC

2. ADT plus docetaxel for mHSPC



While 177Lu-PSMA-617 is currently well-established in the 3rd line mCRPC treatment paradigm, numerous studies are evaluating this agent in earlier line settings. The PSMAfore trial (NCT04689828) is evaluating 177Lu-PSMA-617 in the pre-chemo, 2nd line setting. While results are not yet available, a press-release by Novartis stated that “PluvictoTM shows statistically and clinically meaningful radiographic progression-free survival benefit in patients with PSMA-positive metastatic castration-resistant prostate cancer”. Novel radioligands are currently in clinical development and testing, which is critical when we consider the recent logistic/production issues pertaining to PluvictoTM.

The most notable of these is 177Lu-PSMA-I&T (177Lu-PSMA-PNT2002), which is currently being evaluated in the 2nd line, post-ARPI mCRPC setting within the context of the SPLASH trial.

In addition, theranostics are being evaluated in the mHSPC, BCR, and pre-surgical treatment settings as well.
Finally, theranostics are also currently being evaluated in combination with other agents (e.g. immunotherapy, chemotherapy, PARP inhibitors, monoclonal antibodies, radionuclides such as 225Ac and 233Ra, and ARPIs) as demonstrated in the figure below.

Presented by: Professor Silke Gillessen Sommer, MD, Head of the Medical Oncology Department and Medical Scientific Director of the Oncology Institute of Southern Switzerland (IOSI) at the Ospedale San Giovanni in Bellinzona, Switzerland
Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 European Association of Urology (EAU) Annual Meeting, Milan, IT, Fri, Mar 10 – Mon, Mar 13, 2023.
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