Real-world outcomes after post-Lu177 therapy in mCRPC show limited survival and heterogeneous treatment patterns

ASCO GU 2026

26 - 28 Feb 2026

Published: 6 Mar 2026

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Dr Ben Tran - Peter MacCallum Cancer Centre, Melbourne, Australia,

Dr Ben Tran speaks to ecancer about a real-world study which evaluated outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) who required treatment after lutetium-177 vipivotide tetraxetan (Lu177).

Among 743 patients treated with Lu177, 161 (22%) initiated subsequent therapy, with more than 40 different treatment regimens identified.

The most common regimens were cabazitaxel, cabazitaxel plus carboplatin, and enzalutamide, and about 50% of patients received chemotherapy-based treatment.

Median overall survival from the start of post-Lu177 therapy was 8.0 months overall, with 13.5 months in pre-taxane patients and 6.8 months in post-taxane patients.

Poor performance status (ECOG ≥2) and shorter duration of prior Lu177 treatment (<180 days) were associated with significantly worse survival.

Overall, treatment selection after Lu177 was highly variable and associated with short treatment duration and limited survival, highlighting the unmet need for more effective therapies in the post-Lu177 mCRPC setting.

Lutetium-PSMA is used more and more frequently. Known as Pluvicto, It has demonstrated survival benefit for patients in later line therapy through the VISION study, as well as early line CRPC through PSMAfore. So it’s being used more and more in the clinic now. So for new drugs being developed that are being developed in the post-Pluvicto space, it’s important to understand what the comparator… how well they might do. So our real-world study interrogated the Flatiron database and we looked for patients who had been treated with Pluvicto and examined patients who had treatment following Pluvicto. What we found was the treatments ranged from cabazitaxel to combinations of taxanes and carboplatin and sometimes rechallenge with AR pathway inhibitors.

What we did find is that outcomes are poor in this patient population. Patients who develop disease progression after receiving Lutetium-PSMA do poorly, a median overall survival of only 8 months. Some patients receive Lutetium-PSMA prior to having had chemotherapy and those patients, as you’d expect, do do slightly better, a median overall survival around 12-14 months. Those who have had prior chemotherapy do more poorly, a median overall survival around 6 months.

So it’s important to understand this as we develop clinical trials to help these patients. Patients who have had Pluvicto, we now understand, do poorly and we need to find treatments that help them. By understanding how poorly they do do we can guide our clinical trials towards that.

Do findings suggest an optimal sequencing approach in metastatic castration-resistant prostate cancer?

Our real-world data study was unfortunately not designed to determine if patients should have chemotherapy before Pluvicto or Pluvicto before chemotherapy. We can’t really gain too much information from what we’ve conducted.

What is next for this study?

This is still a small set of patients and we hope to validate it in other real-world populations. I run an Australian registry for prostate cancer called ePAD and we’ll publish some data from ePAD which looks at the same question. The selection criteria for Pluvicto in Australia differs to that from the United States so we’d perform an FDG-PET along with a PSMA-PET, which means approximately 30% of patients are screened out, are deemed not likely to benefit from Lutetium-PSMA. So therefore, as you’d expect, the patients receiving Lutetium-PSMA are a better cohort and we would hopefully report that their outcomes following Lutetium-PSMA are also better than that of the US population.