Lutetium-177–PSMA-617 improves self-reported pain and HRQoL in taxane-naïve patients with PSMA-positive mCRPC

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Published: 2 Jun 2024
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Prof Karim Fizazi - Institut Gustave Roussy, Villejuif, France

Prof Karim Fizazi speaks to ecancer at ASCO 2024 about a study looking at health-related quality of life and pain with the use of lutetium-177–PSMA-617 in taxane-naïve patients with metastatic castration-resistant prostate cancer .

He explains that patients were randomized 1:1 to open-label lutetium-177–PSMA-617 or ARPI change (abiraterone/enzalutamide).

Prof Fizazi reports that self-reported data collected from two questionnaires showed that lutetium-177–PSMA-617 improved time to deterioration in quality of life by approximately 40%.

Lutetium-177–PSMA-617 improves self-reported pain and HRQoL in taxane-naïve patients with PSMA-positive mCRPC

Prof Karim Fizazi - Institut Gustave Roussy, Villejuif, France

I was really delighted to present the data on PSMA-4 which is a phase III trial looking at lutetium-PSMA in patients with metastatic castration resistant prostate cancer who have already experienced cancer progression after an androgen receptor pathway inhibitor. So these patients may go for docetaxel chemotherapy as a standard of care but really in this trial we focussed on patients who are not really candidates for immediate chemotherapy because they had more indolent disease, they had just a few symptoms or no symptoms at all, or they were not really willing to go for chemotherapy immediately.

So for these patients we knew already that lutetium-PSMA was potentially an active treatment thanks to another phase III trial called VISION in more advanced disease, where lutetium-PSMA already improved overall survival and quality of life. So the idea in PSMA-4 was really to test this treatment earlier in the course of the disease.

Patients, again, were randomised in a 1:1 fashion. Either they received lutetium-PSMA immediately or they received a second androgen receptor pathway inhibitor and then at progression they could receive lutetium-PSMA. So it was a nice deal with the patients to get access to treatment either right now or in a different manner.

What the trial showed is that the primary endpoint, which is radiographic progression free survival, is very clearly improved. It’s really doubled, basically, 6 months for the median in the control arm versus more than a year with lutetium-PSMA. A very clear difference, this is really what the agencies, the regulatory agencies, want to see first.

What we also assessed is overall survival because we want to make sure that using a radioligand earlier in the course of the disease does not impact negatively on overall survival in the long term and it’s not the case. The hazard ratio is less than 1.0, this is reassuring.

Third, we looked at quality of life and pain because, of course, not only do we want to do good things for the patients in terms of postponing imaging-based progression, but we want to directly improve patients’ lives, if you will, or avoid deterioration in their quality of life. So quality of life was measured using two different questionnaires and actually the data are very similar. We improved time to deterioration in quality of life by approximately 40% which is good and this is true in terms of physical wellbeing, emotional wellbeing, functional wellbeing, all that is important in quality of life. Also for pain time to deterioration of pain was improved by 30% which is very important in prostate cancer because patients have typically bone metastases which can be painful and that can also develop local progression in their pelvis which can be also associated with pain. So it’s very good to see that we are directly improving patient outcomes.

So we have now a nice picture and this is complemented by the side effects, the safety profile of the drug which is very clean, to be honest. We are improving time to progression of cancer whatever way we measure it – PSA, imaging, quality of life, pain, all this is improved by lutetium-PSMA. Safety is really mostly fine, it’s really mostly non-toxic. In the context of a strong crossover, 80% of patients received crossover to lutetium-PSMA in the control arm, overall survival is not negatively impacted. So we have a nice file, if you will, to convince ourselves and all our colleagues and hopefully the regulatory agencies to have this treatment soon for all our patients.

The next step will be to test this very same treatment even earlier in the course of the disease. For example, for men with metastatic castration sensitive disease the PSMAAddition trial has completed its accrual. We are following these patients and hopefully in one or two years from now we will be able to look at the data.