Research in context
Evidence before this study
We searched PubMed and MEDLINE for peer-reviewed, original studies published in English up to the commencement of our trial design in July, 2015, with the search terms “Lu-177-PSMA”, “Lutetium”, “radioligand treatment”, and “PSMA”. We also reviewed key journals and congress abstracts in the fields of nuclear medicine and urological oncology. We found small retrospective case reports or series suggesting high activity in patients given treatment on a compassionate basis after failing conventional treatments. No prospective data for radionuclide treatment with [177Lu]-labelled PSMA were available. Therefore, we designed a phase 2 prospective trial to investigate the efficacy, safety, and effect on quality of life of this treatment. Several retrospective studies have been published since, but high-quality, prospectively collected data on outcomes and safety are still unavailable.
Added value of this study
This is the first prospective phase 2 study to provide compelling evidence that radionuclide treatment with [177Lu]-PSMA-617 has promising anti-tumour activity, a favourable toxicity profile, and improves quality of life in men with metastatic castration-resistant prostate cancer who have progressed after standard treatments including chemotherapy and second-generation anti-androgens.
Implications of all the available evidence
Collective data from this phase 2 study and several retrospective series, provides proof of concept that [177Lu]-PSMA-617 has promising anti-tumour activity, low toxicity, and improves quality of life in patients with metastatic castration-resistant prostate cancer who have not responded to most conventional treatments and exhibit high PSMA expression on PSMA PET/CT. In view of the almost ubiquitous nature of PSMA expression in most metastatic castration-resistant prostate cancers, [177Lu]-PSMA-617 offers a potential additional treatment option for men with metastatic castration-resistant prostate cancer. Studies comparing [177Lu]-PSMA-617 to existing standards of care, or in combination with other treatments are now required. The evidence from this study formed the basis of a recently commenced Australian multicentre randomised phase 2 trial comparing [177Lu]-PSMA-617 to cabazitaxel (NCT03392428), and several early phase trials combining [177Lu]-PSMA-617 with other new treatments.