Declan Murphy, MB, BCH, BaO, FRACS, FRCS, Urol, Peter MacCallum Cancer Centre, Melbourne, Australia, shares an update on the ongoing Phase II TheraP trial (NCT03392428) investigating cabazitaxel versus 177Lu-PSMA-617 in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). The primary endpoint for the study is prostate-specific antigen (PSA) response. At a median follow-up of 18.4 months, progression-free survival (PFS) was significantly longer in patients treated with 177Lu-PSMA-617 compared with those who received cabazitaxel. The objective response rate (ORR) was also significantly greater in patients who received 177Lu-PSMA-617 at 49% versus 24%. This interview took place during the 2021 Genitourinary Cancers Symposium.
Transcript (edited for clarity)
TheraP is a prospective multicenter randomized controlled trial based here in Australia, comparing cabazitaxel second line chemotherapy with lutetium PSMA for men with progressive metastatic CRPC. So, what we’ve done with lutetium PSMA is take it from terminal or end-stage men with prostate cancer, where we reported a single-arm Phase II study a couple of years ago into the randomized format up against a high quality standard of care and cabazitaxel...
TheraP is a prospective multicenter randomized controlled trial based here in Australia, comparing cabazitaxel second line chemotherapy with lutetium PSMA for men with progressive metastatic CRPC. So, what we’ve done with lutetium PSMA is take it from terminal or end-stage men with prostate cancer, where we reported a single-arm Phase II study a couple of years ago into the randomized format up against a high quality standard of care and cabazitaxel. And the primary endpoint in this study was based on PSA response and other key secondary endpoints like radiographic and clinical progression-free survival and overall survival. And really it was getting quite exciting for us to have the data, the final data from this presented here at the ASCO GU meeting by my colleague, Professor Michael Hoffman, a nuclear medicine physician at Peter MacCallum Cancer Center in Melbourne, and also co-published this week in Lancet, so a major publication. And in summary, what he showed in this trial is that the men undergoing lutetium PSMA therapy had a significantly better PSA response of about 66% compared with about 37% of men in the cabazitaxel arm.
So this is a very positive endpoint, which this trial successfully reached. Of course, we know that PSA as an endpoint is not as clinically meaningful as radiographic and clinical progression-free survival and of course overall survival. And certainly in the key secondary endpoints just mentioned we see significant benefits in clinical and radiographic progression-free survival, but the overall survival endpoint as anticipated has not yet been met.
But I think what we see in this is the therapy is very well tolerated with very good quality of life, much easier tolerated for men than second-line chemotherapy. And so if this dramatic improvement in PSA response does translate into an overall survival advantage, then I expect that this will become a very viable option, very visible in all guidelines because of that attraction of a very well tolerated therapy. So, coming in this space soon will be a trial called the VISION trial, a Phase III study as company supported by the lutetium industry, which will report overall survival, we hope later this year, but in the meantime, TheraP is creating a lot of excitement as a prospective randomized trial in this space.
Declan Murphy, MB, BCH, BaO, FRACS, FRCS, has participated in advisory boards and speaker activities with Janssen, Astellas, Bayer, AstraZeneca, Ferring and Ipsen.