Early data from the LuPIN trial in men with mCRPC

A lot of people are hopeful that treatment with a new form of targeted nuclear radiation therapy — lutetium-177 PSMA 617 (177Lu PSMA) — will be able to significantly extend survival of men with metastatic, castration-resistant prostate cancer (mCRPC) who have already progressed after treatment with drugs like abiraterone acetate (Zytiga), enzalutamide (Xtandi), and taxane-based chemotherapy.

Early data with 177Lu PSMA have shown distinct promise in some — but by no means all — patients, and formal registration trials are in progress. However, we now also have data from the so-called LuPIN trial in Australia showing that when 177Lu PSMA is given in combination with a radio-sensitizing drug known as idronoxil or NOX66 we may be able to expand the number of men who benefit from this type of treatment. The data from this trial show PSA responses of 50 percent and higher in nearly 70 percent of the patients treated to date.

To be clear, these data come from a very early-stage Phase I/II clinical trial in just 16 men (see the abstract of the paper by Emmett et al. just presented at a meeting of the Society for Nuclear Medicine). We also need to be clear that this drug combination (which must also be given in association with dexamethasone) can have some significant side effects.

It will clearly be some time before we can know whether the benefits of combination therapies like this can outweigh the risks, but there are still relatively few effective options for men with mCRPC, so every step forward could be an important one.

One Response

  1. “All men received Dexamethasone 8 mg on Day 1 and 4 mg days 2,3.” These are very high doses of dexamethasone and may be the reason for all of the PSA effect. In mCRPC patients who received just 1.5 mg/day of dexamethasone, PSA decreased by > 50% in 61% of patients in this earlier study (n = 38):

    Compared to this historical (1995) control, there is no evidence for an effect of Lu-177-PSMA-617 here, let alone for idronoxil. However, this was before taxane chemotherapy, and it is entirely plausible that chemotherapy pretreatment may result in diminished potential to get the same magnitude of response to subsequent treatments. If that is the case, it may be that something other than dexamethasone had an effect here. It’s anyone’s guess until there is a randomized trial.

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