Chaired by Prof. Axel Merseburger (DE), Dr. Alison Tree (GB) and Prof. Jan Oldenburg (NO), the game-changing session on day three of EMUC24 was a wrap-up of what has been an exciting year for genitourinary cancer treatment trials, particularly prostate cancer.
PSMAfore and SPLASH
Dr. Riccardo Mei (IT) shared the results of the PSMAfore and SPLASH studies in his presentation ‘Lu-PSMA radioligand therapy in pre-taxane mCRPC patients’. He stated that both the trials enrolled patients with androgen receptor pathway inhibitor (ARPI) pre-treated, progressive metastatic castration-resistant prostate cancer (mCRPC) with evidence of PSMA-avid PET. The radionuclide dose was significantly higher in the PSMAfore trial where patients received 7.4 GBq every six weeks for up to six cycles, versus 6.8 GBq every eight weeks for up to four cycles in SPLASH.
Dr. Mei explained that both trials met their primary endpoint of a radiographic progression-free survival benefit, although the magnitude of benefit was greater in PSMAfore (HRs: 0.43 versus 0.71 for SPLASH). Both trials demonstrated a health-related quality of life benefit for Lu PSMA. “PSMA RLT reduced the risk of radiographic progression versus an ARPI switch in taxane-naive patients. Lower dose and longer intervals seem to reduce response with only some reduction in the incidence of side effects, particularly dry mouth and anaemia.”
In Dr. Mei’s opinion, there are many questions yet to be answered about the timing of treatment, optimal dosing, number of cycles of Lu-PSMA, combined/tailored treatment, new isotopes (alpha emitters, auger emitters), as well as therapy selection when considering tumour burden, number of treatments, aggressive/indolent disease, genetic profile etc.
PEACE-3
“ENZA (enzalutamide) + Ra223 (radium-223 dichloride) is the first ARPI combination to show statistically significant improvement in both radiographic progression-free survival (HR 0.69) and overall survival in bone metastatic castration-resistant prostate cancer”, stated medical oncologist Dr. Fabio Turco (CH) in his presentation where he shared the recent results of the PEACE-3 trial.
PEACE-3 is a randomised, open-label phase III trial investigating the combination of radium-233 and enzalutamide in asymptomatic or mildly symptomatic patients with bone mCRPC. Dr. Turco defined radium-223 as an alpha-particle-emitting calcium mimetic that selectively targets bone metastases and induces double-stranded DNA-breaks. He explained that the study design comprised enrolment of 426 patients across 12 counties from 2015 to 2023. Eligible patients who had castration-resistant PCa with bone metastases were asymptomatic or mildly symptomatic, and had not received prior treatment with enzalutamide, apalutamide, darolutamide, or radium-223.
According to Dr. Turco, the addition of Ra223 to enzalutamide was associated with significant improvements in the primary endpoint of radiographic progression-free survival (median: 19.4 versus 16.4 months; HR: 0.69) and there was an overall survival benefit of 42.3 months for ENZA + Ra223 versus 35 months for enzalutamide monotherapy.
“The trial results support the combination of ENZA + Ra223 (plus a bone density protecting agent) as a potential new first line mCRPC treatment option for patients with prostate cancer and bone metastases who have not received a prior-androgen-receptor pathway inhibitor”.
GETUG-AFU 18
Radiation oncologist Prof. Christophe Hennequin (FR) presented on the GETUG (French Genito-Urinary Tumour Group) 18 trial evaluating the impact of radiotherapy therapy dose escalation (80 versus 70Gy) in high-risk prostate cancer patients receiving long-term androgen deprivation therapy (ADT). Prof. Hennequin stated that 505 patients from 25 French centres were included in the trial. Over a median follow-up of 9.5 years, the biochemical or clinical progression-free survival was significantly improved in the dose-escalated radiotherapy arm compared with conventional radiotherapy arm (HR 0.56). There were also significant differences in prostate cancer-specific survival (HR 0.48) and improved overall survival (HR 0.61).
In his closing summary of the trial results, Dr. Hennequin concluded that even in the case of long-term ADT, higher dose radiotherapy (80 Gy) improved progression-free survival, prostate cancer survival and overall survival among patients with high-risk prostate cancer. “These efficacy results were achieved with no increase in toxicity. High dose radiotherapy with long-term ADT is a new standard of care in the management of high risk localised prostate cancer.”
You can watch the full presentations via webcast recordings at the EMUC24 Resource Centre.
