Scott T. Tagawa, MD, MS, Weill Cornell Medical College, New York Presbyterian Hospital, NY, discusses the updated results from the VISION trial (NCT03511664); a Phase III study investigating the efficacy of the beta emitter 177Lu-PSMA-617 in prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). 177Lu-PSMA-617 improved progression-free survival (PFS) and overall survival (OS) of patients. Toxicity was greater in patients treated with both 177Lu-PSMA-617 and best standard of care (BSOC) than in patients treated with BSOC alone. The results from this study may facilitate the worldwide, accessible, approval of 177Lu-PSMA-617 and enable its deployment as an early-stage therapeutic approach against mCRPC. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 virtual meeting.
Transcript (edited for clarity)
As most of you all know the Vision study was a study of lutetium PSMA-617. PSMA-617 is a small molecule that targets PSMA. Lutetium 177 is a beta emitter. This was a late stage pretreated patient population designed to be post potent AR and chemotherapy, mostly patients with all available chemotherapy done. Although one of the entry criteria could have been ineligible for cabazitaxel. But basically it was standard of care other than radium or cytotoxic chemotherapy...
As most of you all know the Vision study was a study of lutetium PSMA-617. PSMA-617 is a small molecule that targets PSMA. Lutetium 177 is a beta emitter. This was a late stage pretreated patient population designed to be post potent AR and chemotherapy, mostly patients with all available chemotherapy done. Although one of the entry criteria could have been ineligible for cabazitaxel. But basically it was standard of care other than radium or cytotoxic chemotherapy. So mostly AR targeting agents, but it could include steroids or extraordinary radiation or things like that. So it was randomized, that standard of care with or without. So it was a kind of a two plus one type of study and a two to one design with dual primary end points of RPFs and OS and the bottom line … and this was a selected patient population with PSMA PETs.
Although for those that are familiar with the therapy study, the criteria to get in were much less strict. And I think that’s reflected when people look at the results of who was excluded for not having PSMA positivity. It was a small minority in this study, as opposed to about almost 30% in therapy. But overall, as I think people know, a positive study so both RPFs, as well as overall survival were improved. There was more toxicity in the two treatment, meaning lutetium 617 plus standard of care had more AEs than standard of care alone. That’s not surprising because it’s two versus one and patients who were on the dual arm a lot longer than they were the same arm. So overall, I would say it confirms what, at least in my bias view point, many of us expected that this type of an approach will work. So what my hope is that will lead to worldwide approval of the agents in a way that’s accessible and paid for by whatever kind of insurance is available in each country.
And this particular drug, as well as others, are now moving an earlier line of therapy in randomized trials. So there are actually at least four that I know of phase three trials that are either much earlier lines of therapy, such as the AFT 53, it’s an addition study, which is frontline hormone sensitive, ADT plus AR pathway inhibitor with or without lutetium PSMA-617 upfront versus at progression. So it’s a crossover study with an RPFS endpoint. There are two studies in that initial post AR setting. One with 617 and one with PNT2002. That is a trial progress that’s being presented called SPLASH. And then lutetium J51 AKA TLX591 just launched a study in Australia that’s coming to the United States. One step later in terms of post those attacks. Also, it’s great that we have now two randomized trials that are positive, a phase two and a phase three. And hopefully that’s going to lead to an approval and this is on the heels of imaging approvals. And hopefully it’ll be additional phase three approvals.