Combining LuPSMA with pembrolizumab ‘promising’ for mCRPC
medwireNews: Results of the PRINCE trial point to the potential of lutetium-177-prostate-specific membrane antigen-617 (LuPSMA) plus pembrolizumab for the treatment of metastatic castration-resistant prostate cancer (mCRPC) with high expression of PSMA.
Presenting the findings at the ESMO Congress 2021, Shahneen Sandhu, from Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia, said that the radiolabeled small molecule has demonstrated beneficial outcomes in both the TheraP and VISION studies of patients with mCRPC.
She reported an interim analysis of the phase 1b proof-of-concept study, which included 37 patients with mCRPC who had PSMA-avid disease, defined as a maximum standard uptake value (SUVmax) of 20 or more at one site, an SUVmax of 10 or more at other sites, and no fluorodeoxyglucose-positive or PSMA-negative sites of disease. All patients had progressed on a novel hormonal agent and 70% had previously received docetaxel.
They were given LuPSMA at 8.5 GBq every 6 weeks with a 0.5 GBq reduction at each cycle (maximum six cycles, median four) plus pembrolizumab 200 mg every 3 weeks (maximum 35 cycles, median eight), and followed up for a median of 38 weeks.
The combination demonstrated “promising activity” according to Sandhu, with a decline in prostate-specific antigen (PSA) levels of at least 50% observed in 73% of patients and a partial response in seven of the nine patients with RECIST-measurable disease, giving an objective response rate of 78%.
The rates of radiographic progression-free survival (PFS) and biochemical PFS at week 24 were 65% and 68%, respectively.
Sandhu said that the adverse event (AE) profile was consistent with that of single-agent LuPSMA and pembrolizumab, with the most common grade 3 treatment-related AEs being fatigue in two patients, and anemia and amylase increase in one patient each. There were no grade 4 AEs or treatment-related deaths.
Toxicities led to 11% of patients discontinuing pembrolizumab, but none led to discontinuation of LuPSMA.
The most common grade 3 immune-related AE was colitis, in two patients, followed by one case each of amylase elevation, pancreatitis, nephritis, type 1 diabetes, mucosal pemphigus, ocular myasthenia gravis, and pneumonitis.
Sandhu emphasized that “further follow-up is needed to define the impact of pembrolizumab on radiological progression-free survival and overall survival.”
And she concluded: “Biomarker analysis is ongoing to understand the effects of [LuPSMA]and pembrolizumab on the tumor microenvironment and to define predictors of response and resistance.”
Discussant Joaquin Mateo (Vall d’Hebron Institute of Oncology, Barcelona, Spain) noted that the combination does appear to achieve a much higher response rate than pembrolizumab alone, but he stressed that “we will need to wait for longer follow-up to see if there is any impact in time to progression.”
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