The novel radioactive treatment Lu-PSMA offers tolerability but no survival advantage over current standard-of-care cabazitaxel chemotherapy for people with metastatic castration-resistant prostate cancer (mCRPC), latest findings from the Australian-led TheraP trial show.
Three year follow up data presented at ASCO 2022 show that no difference in overall survival but patients receiving Lu-177–PSMA-617 radioligand therapy had fewer adverse events and better patient-reported outcomes compared with patients treated with cabazitaxel, said study investigator Professor Michael Hofman of the Peter Mac Cancer Centre, Melbourne.
The Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group study enrolled 200 patients with mCRPC progressing after docetaxel to receive either up to six cycles of LuPSMA administered at a dose of 6.0–8.5 GBq every six weeks or a maximum of 10 cycles of cabazitaxel 20 mg/m2 every three weeks.
Previous results from the study showed that those assigned to LuPSMA had significant improvements in PSA response rate, progression-free survival and less Grade 3-4 toxicities as well as better patient-reported outcomes.
Presenting the overall survival (OS) results at ASCO, Professor Hofman reported that at 36 months OS was similar in those assigned to LuPSMA versus cabazitaxel (mean survival time 19.1 vs. 19.6 months, difference -0.5, 95% CI -3.7 to + 2.7).
Survival was considerable shorter for 61 people who were screened for the trial but for whom treatment was not suitable because PSMA uptake was low on initial scans or had FDG discordance (11 months compared to 18.8 months for those on trial treatments).
No additional safety signals were identified with longer follow-up.
Professor Hofman concluded that the three-year follow-up of the TheraP study “provides compelling evidence that Lutetium-177 PSMA-617 is a new treatment option for people with prostate cancer, providing an alternative to cabazitaxel chemotherapy with better patient reported outcomes and lower side effects.”
“The TheraP data supports the choice of 177Lu-PSMA-617 over cabazitaxel for patients with PSMA-positive, progressive mCRPC after docetaxel and androgen-receptor pathway inhibitor, on the basis of its higher PSA response rate, greater PFS benefit, quality of life benefits, favourable safety profile, dosing schedule six weeks vs three weeks, and similar survival outcomes to cabazitaxel,” he said
This unique treatment involved two distinct parts. Firstly, a PET scan is used to ‘map’ the cancer. This is done by injecting a radioactive molecule called gallium-68 attached to a small molecule that rapidly localises to prostate specific membrane antigen (PSMA) on the surface of prostate cancer cells in the body.
The result is the cancer cells ‘light up’, showing exactly where the disease is and enabling identification of patients that may benefit from this new therapy.
The second part is the therapy itself: the Lu-177 radionuclide is attached to a similar molecule used in the scanning process, and LuPSMA is administered to the patient, targeting the tumours and killing the cancer cells while minimising damage to surrounding tissue.
ANZUP Chair Professor Ian Davis said the latest findings provided lessons on “how this novel and important LuPSMA therapy can be used most effectively.”
“The findings from the TheraP three-year follow-up study add to a growing body of clinical evidence that Lutetium-177 PSMA-617 is a safe, effective, and superior treatment for people with advanced prostate cancer,” he said.