Among patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with lutetium Lu 177 vipivotide tetraxetan (Pluvicto), the radiographic progression-free survival (rPFS) was comparable with that reported in the overall study population, regardless of disease volume and de novo/recurrent status, according to a set of subgroup analyses from the phase 3 PSMAddition trial (NCT04720157).
“Reassuringly, we saw for the rPFS primary end point that [patients in] all 4 categories, whether high or low volume, de novo, or recurrent, were benefiting to similar degrees [from lutetium Lu 177 vipivotide tetraxetan]. [These findings were consistent with those] of the overall study,” Fred Saad, MD, CQ, FRCS, FCAHS, the director of prostate cancer research at Montreal Cancer Institute and a full professor in the Department of Surgery at the Université de Montréal in Canada, said in an exclusive interview with OncLive®.1
In the interview, Saad discussed the background of the PSMAddition trial; findings from the subgroup analyses, which he presented during the 2026 ASCO Annual Meeting; and how these data may affect clinical practice.
Key Takeaways From the Subgroup Analyses of PSMAddition
- Adding lutetium Lu 177 vipivotide tetraxetan to an ADT/ARPI improved rPFS across subgroups in PSMAddition, with consistent benefit in patients with high- and low-volume disease and those with de novo or recurrent mHSPC.
- Secondary efficacy outcomes and safety findings were broadly consistent across patient groups, with delayed PSA progression, favorable trends toward delaying mCRPC, preserved quality of life, and no increase in adverse effects among low-volume patients.
- The data support broader use of the regimen but highlight the need for individualized treatment decisions for low-volume disease, where factors such as metastatic burden, age, life expectancy, and advanced imaging may help refine patient selection.
OncLive: What prior data have been reported to date from PSMAddition?
Saad: PSMAddition [was designed] to see whether we could improve on what most would consider the best standard of care for patients with mHSPC, which would be androgen deprivation therapy [ADT] plus an androgen pathway receptor inhibitor [ARPI].2 In the study we randomly assigned patients with prostate-specific antigen [PSA]–positive disease to ADT/ARPI as a control arm or ADT/ARPI plus lutetium Lu 177 vipivotide tetraxetan. This was a 1:1 random assignment with a primary end point of rPFS. [The study] reached its primary end point with a HR of 0.72 [95% CI, 0.58-0.90; P = .002], which was a statistically significant improvement in delaying radiographic disease progression [or death].
What were the key findings from the subgroup analyses that you presented during ASCO?
We wanted to look at whether there were differences in patients with high- or low-volume disease and in patients with de novo or recurrent mHSPC.1 For the rPFS end point… HRs ranged from 0.72 to 0.74, [which was] in the range of the overall [population]. This was very reassuring.
We [also analyzed] time to PSA progression; this was improved across the board, similar to the overall results of the study time to mCRPC. We're seeing the same trend across the board for the low-volume patients. Approximately 32% [of patients] were low volume. [There was a] short [period of] follow-up, so it’s still too early to figure out the magnitude [of benefit] in these low-volume patients, but overall rPFS was improved across the board.
Reassuringly, quality of life [was] similar to the overall results of the study, and the adverse effect [AE] profile was also similar regardless of whether patients were low or high volume. We aren’t harming low-volume patients more than the high-volume patients, which could have been a concern given the fact that we're [potentially] giving a lot of drug in a low-volume scenario. However, there really was no difference in AEs, so this was very reassuring.
How do these data from the subgroup analyses add to our understanding of which patients derive the greatest benefit from an ADT/ARPI and lutetium Lu 177 vipivotide tetraxetan?
That’s an important question. Would I treat all low-volume [patients with this approach]? I think many low-volume [patients], depending on age [and] life expectancy, can do probably very well with just ADT and ARPI. This is where shared decision-[making] and individualizing care, [are important].
There are a wide spectrum of low-volume patients. [A patient] can have 10 bone metastases in their spine, and they’d still [be considered] low volume because it's all in the axial skeletal. There's a difference between 1 or 2 bone metastases and some lymph node metastases vs 10 to 15 bone metastases in the spine [or] in the pelvic area. I think we have to refine [this distinction] a bit more, and we're starting to use other methods besides this crude low- and high-volume categorization. We're starting to use PET scanning to try to estimate true volume of disease, rather than imaging based on PSMA. This is a field that's going to continue to mature.
References
- Saad F, Tagawa ST, Sartor AO, et al. Subgroup analyses by disease volume and de novo/recurrent mHSPC in the PSMAddition study of [177Lu]Lu-PSMA-617. J Clin Oncol. 2026;44(suppl 16):5020. doi:10.1200/JCO.2026.44.16_suppl.5020
- Tagawa S, Sartor O, Piulats J, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Ann Oncol. 2025;44(suppl 2): S1627-S1628. doi: 10.1016/j.annonc.2025.09.101
