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 fewer 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 fewer symptoms in multiple domains with 177Lu-PSMA617 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 updated study results from the TheraP study will be available online on Thursday 11 February 10:15 AM-11:15 AM Eastern/Friday 12 February 2.15 AM - 3.15 AM AEST as an Oral Presentation Session and Panel Discussion (Progress and Promise in Treatment Personalization for Advanced Prostate Cancer) at the American Society of Clinical Oncology (ASCO) Annual Scientific Genitourinary Cancers Virtual Symposium.
Source: Anzup.org.au. 2021. ANZUP - Improving outcomes for Bladder, Kidney, Testicular, Penile and Prostate Cancers.
[¹⁷⁷Lu]Lu-PSMA-617 Versus Cabazitaxel in Patients with Metastatic Castration-Resistant Prostate Cancer (TheraP): A Randomised, Open-Label, Phase 2 Trial
ANZUP Mini ASM 2020: The Global Context of the TheraP Trial and the Pathway to Approval
TheraP: 177Lu-PSMA617 Theranostic vs Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer (mCRPC) - Michael Hofman & Ian Davis
ASCO GU 2021: 177Lu-PSMA-617 Versus Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer Progressing After Docetaxel: Updated Results Including Progression-Free Survival and Patient-Reported Outcomes (TheraP ANZUP 1603)
Clinical Trial Information: NCT03392428