An Australian phase 2 trial may be a game changer for men with prostate cancer by combining precision nuclear medicine and immunotherapy approaches, study investigators say.

The EVOLUTION study aims to recruit 100 men with metastatic castration-resistant prostate cancer (mCRPC) to evaluate a combination of Lutetium-177-PSMA (Lu-PSMA) and two immunotherapy drugs, ipilimumab and nivolumab.

The rationale for the trial is to investigate whether radionuclide therapy may enhance the efficacy of immunotherapies that -unlike other cancers – have so far shown only limited benefit against prostate cancer.

“The reasons for this are not known, but we believe it could be made more effective if we think creatively about how it is given,” says Professor Ian Davies, chair of the The Australian and New Zealand Urogenital and Prostate Cancer Trials Group that is running the trial in conjunction with  the PCFA.

“Radiotherapy has been shown to help boost the immune response in other settings so it is possible that combining radiotherapy with immunotherapy might lead to more and better responses in prostate cancer,” he said.

A/Prof Shahneen Sandhu

Principal investigator Associate Professor Shahneen Sandhu, a medical oncologist at a consultant medical oncologist and researcher in the melanoma and uro-oncology units at the Peter MacCallum Cancer Centre, Melbourne said ipilimumab and nivolumab would be added to the radionucleide treatment attaches itself to the prostate specific membrane antigen (PSMA).

The radiotracer Lutetium is usually given in intervals of six weeks, with between four and six cycles of the treatment recommended.

“Recent studies have shown that Lu-PSMA is a promising treatment for men with metastatic prostate cancer that is no longer under control after several standard treatments. The aim of this study is to see if combining ipilimumab and nivolumab with Lu-PSMA can further improve the anti-cancer effects of Lu-PSMA,” she said.

“It is thought that ipilimumab and nivolumab and Lu-PSMA may work together to treat the cancer. Lu-PSMA can potentially kill cancer cells and break up the tumour into small pieces that may be recognised by [the] immune system while ipilimumab and nivolumab helps [the] immune system to be activated to find and attack [the] cancer.”

The Prostate Cancer Foundation of Australia (PCFA) has invested $1.6 million in funding for the EVOLUTION Trial in the hope that the new treatment combination may lead to shrinkage or stabilisation of previously progressing tumours and therefore hopefully stop or reverse the growth of mCRPC.

“We are on the verge of a complete transformation in prostate cancer treatment, giving men with the most aggressive and deadly forms of this disease a greater hope of survival,” said CEO Anne Savage.

“This trial will go beyond where any other trial has gone before, exploring the next frontier in precision nuclear medicine for prostate cancer, combining Lu-PSMA with immunotherapy, which we think will be a game-changer in the treatment of advanced prostate cancer.”

Ms Savage said the PCFA had successfully advocated for PSMA PET/CT scanning to be listed on Medicare, which will happen from the 1st of July. It is now advocating for Lu-PSMA treatment to be made available to all men who need it, with no out-of-pocket costs. It currently costs $10,000 per round.

“PCFA’s long-term partnership with ANZUP has established Australian researchers as global leaders in this field and enabled more Australian men to live longer with prostate cancer, while undergoing new forms of treatment that have minimal side-effects compared to standard of care,” she said.