GU Cancers 2021 | TheraP: LuPSMA versus cabazitaxel for prostate cancer
Michael Hofman, FRACP, MBBS, Peter MacCallum Cancer Centre, Victoria, Australia, gives an update on the Phase II TheraP trial (NCT03392428) comparing 177Lu-PSMA-617 (LuPSMA) with cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) who progress after docetaxel therapy. 200 patients with mCRPC were enrolled in the study. At a median follow-up of 18.4 months, progression-free survival was significantly longer for patients who received LuPSMA compared to those who received cabazitaxel. This interview took place during the 2021 Genitourinary Cancers Symposium.
Transcript (edited for clarity)
The TheraP study is a randomized Phase II study conducted at 11 sites around Australia, a 200 patient study, as sponsored by the ANZUP Cancer Trials Group. So, an investigator-led cooperative group trial. A randomized trial comparing lutetium-PSMA-617, compared to cabazitaxel chemotherapy.
Lutetium-PSMA-617 is a radiolabelled small molecule that binds to prostate-specific membrane antigen, which is overexpressed on prostate cancer cells, enabling delivery of high doses of beta radiation to sites of tumors wherever they are in the body...
The TheraP study is a randomized Phase II study conducted at 11 sites around Australia, a 200 patient study, as sponsored by the ANZUP Cancer Trials Group. So, an investigator-led cooperative group trial. A randomized trial comparing lutetium-PSMA-617, compared to cabazitaxel chemotherapy.
Lutetium-PSMA-617 is a radiolabelled small molecule that binds to prostate-specific membrane antigen, which is overexpressed on prostate cancer cells, enabling delivery of high doses of beta radiation to sites of tumors wherever they are in the body. The lutetium has a one millimeter path length in seven day half-life. And so it’s very effective at targeting tumor tissues with limited damage to normal tissues.
And this was the first randomized controlled trial. And the primary endpoint was a PSA decline of 50% or more. And that occurred in 66% of men randomized to lutetium-PSMA-617 compared to not only 37% with cabazitaxel. That’s in our intention to treat analysis. That’s a large difference in that primary endpoint.
In this presentation, we also have reported the radiographic progression-free survival and PSA progression-free survival. Those combined had a hazard ratio of 0.63, favoring lutetium-PSMA-617. This difference was most marked at 12 months where 19% in the lutetium-PSMA arm had not progressed, compared to 3% in the cabazitaxel arm. Again, a large difference favoring lutetium-PSMA.
Now we were able to assess objective response rates on CT scanning using the RECIST, and that was seen in 49%. That compared to 24% with cabazitaxel. And importantly, despite these efficacy results, which strongly favor lutetium-PSMA, we saw less adverse events and better patient-reported outcomes with lutetium therapy.
So grade three to four adverse events were seen in 33% versus 54%, low incidence with lutetium. And we did a lot of patient-reported outcomes. And this showed large differences favoring lutetium-PSMA with regards to fatigue, diarrhea, hair loss, insomnia, skin rash, sore hands or feet, or urinary symptoms.
So, the summary of the TheraP trial is that lutetium-PSMA-617 appears to be a new, effective arm of treatment for men with metastatic castration-resistant prostate cancer. And it really appears as promising compared to cabazitaxel chemotherapy.
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