The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) reports the three-year follow up results of its TheraP (ANZUP 1603) clinical trial at the American Society of Clinical Oncology (ASCO) Annual Scientific Virtual Meeting in Chicago on 5 June 2022.
TheraP is the first randomised trial comparing 177Lu-PSMA-617 (Lu-PSMA), a novel radioactive treatment, to the current standard-of-care chemotherapy called cabazitaxel for people with metastatic castration-resistant prostate cancer. These people had disease that had already progressed after standard chemotherapy.
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 Lu-PSMA is administered to the patient, targeting the tumours and killing the cancer cells while minimising damage to surrounding tissue.
The primary endpoint of the study was to compare the effects of the two treatments on change in PSA, a blood biomarker of prostate cancer. The results of the three-year follow up conclude a continued favourable response, defined by reduction of PSA by 50% or more, occurred in 66% of people assigned to receive Lu-PSMA compared to 37% with cabazitaxel. Results of the trial also demonstrated the treatment had less severe side effects than chemotherapy. The survival of people assigned to LuPSMA was similar to cabazitaxel, a proven life-prolonging treatment. Survival was considerable shorter for people screened for the trial but for whom treatment was not suitable because PSMA uptake was low on initial scans (11 months compared to 18.8 months for those on trial treatments).
Study Chair Prof. Michael Hofman, of the Peter MacCallum Cancer Centre, said “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.”
“TheraP is a great partnership of researchers, scientists, supporting organisations, and the patients who participated and who are affected by prostate cancer. These most recent findings show that we continue to learn more about prostate cancer and how this novel and important LuPSMA therapy can be used most effectively,” said ANZUP Chair Professor Ian Davis.
“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. PCFA and its collaborators will continue to support ongoing research into nuclear medicine theranostics for the management and treatment of prostate cancer. The application of Lu-PSMA therapy represents a substantial step forward for the management of advanced prostate cancer in the 21st century,” said PCFA CEO Anne Savage.
Further trial information can be found here.
The ASCO Post with Alicia Morgans and Michael Hofman: https://ascopost.com/videos/2022-asco-annual-meeting/alicia-morgans-and-michael-hofman-on-prostate-cancer-new-data-on-lupsma-vs-cabazitaxel/
ASCO Daily News – https://dailynews.ascopubs.org/do/10.1200/ADN.22.201044/full/
The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) reports the results of its “TheraP” (ANZUP 1603) clinical trial at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Virtual Symposium.
TheraP is the first randomised trial comparing 177Lu-PSMA-617 (Lu-PSMA), a novel radioactive treatment, to the current standard-of-care chemotherapy called cabazitaxel for men with metastatic castration-resistant prostate cancer. These men had disease that had already progressed after standard chemotherapy.
This unique treatment involves first “mapping” the cancer with a PET scan, then treatment with a radioactive substance Lutetium-177 attached to a similar molecule as used for the PET scan. This novel dual approach of imaging and treatment is called “theranostics.”
The primary endpoint of the study was to compare the effects of the two treatments on change in PSA, a blood biomarker of prostate cancer. A favourable response, defined by reduction of PSA by 50% or more, occurred in 66% of men assigned to receive 177Lu-PSMA-617 compared to 37% with cabazitaxel chemotherapy.
177Lu-PSMA-617 also delayed the time to progression defined by a rise in PSA or progression on CT or bone scans. Patients assigned to receive 177Lu-PSMA-617 were 37% less likely to progress. At 12 months, 19% of men assigned to 177Lu-PSMA-617 had not progressed, compared to 3% with cabazitaxel. Objective response rate, a measure of tumour shrinkage on CT scanning, occurred in 49% assigned to receive 177Lu-PSMA-617 compared to 24% with cabazitaxel.
177Lu-PSMA-617 resulted in less side effects to patients than cabazitaxel. Severe adverse effects (grade 3-4 toxicities) reported by physicians occurred in 33% with 177Lu-PSMA-617 compared to 54% with cabazitaxel. Patients reported less symptoms in multiple domains with 177Lu-PSMA-617 including hair loss, diarrhea, fatigue, insomnia, dizziness, urinary symptoms, sore hands/feet and skin rash.
Study Chair Prof. Michael Hofman, of the Peter MacCallum Cancer Centre, said “The theranostics imaging test enables selection of men likely to benefit, whilst the treatment kills tumours and spares normal tissues. This new class of targeted treatment offers men quality of life and better response rates than chemotherapy. It is likely to be available globally in the next 2 years.”
“TheraP is the first trial in the world comparing Lu-PSMA to an active and effective treatment, and has provided evidence that Lu-PSMA might be a good alternative option to chemotherapy for men with advanced and pre-treated prostate cancer. This is the culmination of years of work by a large team of clinicians, researchers, and community representatives,” said ANZUP Chair Professor Ian Davis.
“We are proud to partner with ANZUP on this cutting-edge clinical trial. Deaths from prostate cancer are avoidable, and research is key to saving lives. The interim findings from the TheraP trial demonstrate the tremendous value of Australian-based prostate cancer research towards a future free of prostate cancer,” said PCFA CEO Professor Jeff Dunn AO.
TheraP (ANZUP 1603) is a partnership between ANZUP Cancer Trials Group and the Prostate Cancer Foundation of Australia (PCFA) with support from the Australian Nuclear Science and Technology Organisation (ANSTO), the Australasian Radiopharmaceutical Trials Network (ARTnet), Endocyte Inc, a Novartis company, It’s a Bloke Thing, Movember and CAN4CANCER and The University of Sydney NHMRC Clinical Trials Centre providing central study coordination.
The details were published simultaneously in The Lancet here.
- View the ASCO GU 2021 TheraP presentation here
- View the ASCO 2020 TheraP presentation here
- Watch the Channel Nine news story on our TheraP trial here
- Watch the UroToday interview with Alicia Morgans here
- Listen to the 3AW Melbourne interview here
- UroToday Best of ASCO 2020 Prostate Cancer Podcast with Oliver Sartor featuring TheraP here
- (TheraP is discussed between timepoints 13:13 to 18:47)