mCRPC: The TheraP Trial
A review of recent data from the TheraP trial.
Alicia Morgans, MD, MPH: Another study that informs this clinical space is the TheraP trial. Ulka, I’m going to ask you to walk us through this. As you’re talking through this, we’ll also ask Phil to comment on how patients were selected because that was a little different from VISION.
Ulka Vaishampayan, MD: TheraP was a randomized phase 2 trial of 177-lutetium-PSMA [prostate-specific membrane antigen]–617 as compared with cabazitaxel chemotherapy agent, taxane based, in progressive metastatic CRPC [castrate-resistant prostate cancer]. [To be eligible] patients had to have prior docetaxel and metastatic CRPC, and they had to be eligible for cabazitaxel. [They had to have] reasonable performance status, adequate marrow function, liver function, etc. I’ll ask Phil to comment on the PSMA testing done along with FDG [fluorodeoxyglucose] PET [positron emission tomography] to determine eligibility for this study.
Phillip J. Koo, MD: The Australian team deserves a lot of kudos for pushing the envelope and trying to investigate ways to do things better. No. 1, they introduced 2 radiotracers into this idea of patient selection, so PSMA PET determined whether it’s positive or negative, but also including FDG PET-CT into the work-up. We know prostate cancer is heterogeneous, and the data clearly showed that prostate cancer is very heterogeneous. In those patients who are PSMA positive, there’s discordance between PSMA expression and FDG utilization that maybe these patients wouldn’t benefit from PSMA. This speaks volumes about the heterogeneity and also speaks volumes about how aggressive disease can become in certain cell lines and how it will be different in the body. It also introduced the idea of quantitation. Rather than using just a binary visual approach to a lesion, it said, “Why don’t we use the tools that we have, and if the amount of SUV [standardized uptake value] matches above a certain threshold, then we’ll categorize that as positive. If it’s below a certain threshold, we’ll categorize it as negative.” It took us a step forward, but with this comes a lot of questions. How do we set the thresholds? How do we determine discordance? These are very interesting questions, and we’ll learn more over the years to come.
Ulka Vaishampayan, MD: Excellent points. Also, what this staging mechanism did is select much more stringently patients who are likely to have PSMA expression. Then they were randomized to get the lutetium-PSMA-617 as compared with cabazitaxel at a dose of 20mg /m2—the standard starting dose—and they were stratified. Patients were stratified with disease burden of 20 sites or more or less prior enzalutamide or abiraterone and then study site or location.
Here are the results of the TheraP trial showing that patients with the PSMA-lutetium therapy did significantly better as compared with cabazitaxel therapy. It’s a smaller study, but if you look at the PSA [prostate-specific antigen] response plot, clearly PSMA-lutetium had a much higher chance of PSA response: 66% of patients, compared with 37% with the cabazitaxel, had a PSA reduction of 50% or more.
The second graph shows the radiographic progression-free survival, and it also appears to be improved with the PSMA-lutetium. The hazard ratio is 0.63, and P value is statistically significant favoring the PSMA-lutetium therapy. In terms of adverse effects, not too many surprises there. Fatigue, pain, dry mouth, some diarrhea, and nausea were seen with PSMA-lutetium. Cabazitaxel showed its cytotoxicity with cytopenia as well as diarrhea incidents that were seen with the cabazitaxel. Neuropathy was fairly small: 10% with lutetium-PSMA and 26% with cabazitaxel. Otherwise, the dry mouth and renal dysfunction were seen with lutetium-PSMA.
Alicia Morgans, MD, MPH: Thank you for walking us through that. Tanya, thinking about both these studies, the CARD and TheraP trials, what’s your reaction? It’s a complex space. What are your thoughts in terms of treatment?
Tanya Dorff, MD: When these data were presented, they knocked my socks off. Coming on the heels of CARD, which already elevated how we viewed cabazitaxel as being a really effective agent, you have this trial—somewhat smaller but well designed and clearly showing that lutetium-177-PSMA is even more effective than cabazitaxel, which is already effective. There’s some criticism of the VISION trial in terms of how active the control arm was. Therapy answers that question, that it’s truly a very active treatment. We’re so glad that we can start offering it to our patients relatively soon now that it’s FDA approved.
Transcript edited for clarity.
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