Transcript: PSMAfore: HRQoL and Pain

Declaration of sponsorship Pfizer

Last updated:31st Jul 2024

Published:31st Jul 2024

Dr Neeraj Agarwal, Professor Karim Fizazi, Dr Bárbara Vieira Lima Aguiar Melão, and Professor Axel Merseburger

All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.

And this will be on health-related quality of life and pain in phase 3 study of Lutetium-PSMA-617 in taxane-naive patients with metastatic CRPC, which was the PSMAfore trial presented by Dr Fizazi just recently. And let's hear from him what he thinks about the data.

Thanks, Neeraj. Yes, I think PSMAfore is an important phase 3 data, although I recognise I'm biassed here. So basically, that's the second phase 3 trial looking at the role of lutetium PSMA in men with metastatic castration-resistant disease. We learned already from VISION three years ago that for patients who have exhausted basically every treatment for their prostate cancer, including castration, but also taxane and an AR pathway inhibitor, lutetium PSMA prolonged life, improves radiographic progression-free survival, and also prolongs the time to deterioration of quality of life. And this is becoming more and more, I think, a standard of care for men with very advanced disease. I think I'm happy to speak about that with you, guys, but I think we are using a real lutetium PSMA once available obviously in all respective countries in this indication. So this is what we knew.

Then PSMAfore really address the question as to whether we should use lutetium PSMA earlier in the course of a disease, i.e., in patients with metastatic castration-sensitive disease, but who have not received chemotherapy and who are just progressing while on an AR pathway inhibitor. So typically, a population of men where either you go for chemotherapy if they have aggressive disease, rapidly rising PSA, clinical deterioration or symptoms, or visceral metastasis, for example. Or you are in a situation where there's no fantastic standard to be honest when they have more indolent disease. And typically, you speak about chemo, but you don't use it immediately at least. And actually, this is quite a lot of men who are in the situation and who are demanding something but chemo. So really, PSMAfore addressed the question of lutetium PSMA for vast population of men with more indolent mCRPC. And what we did was we randomised these patients to receive the either lutetium PSMA immediately or a second AR pathway inhibitor, understanding that in case of a progression, patients would be available for crossover to lutetium PSMA. So I guess for the patient, it was a nice deal of lutetium PSMA today versus lutetium PSMA tomorrow. Tomorrow, meaning in six months time, which is basically the time it took for them to progress in the control arm.

So the trial is positive, but the graphic progression-free survival was significantly improved with approximately a 60% reduction in the risk, and this was already presented last year with ESMO. What we showed ASCO was whether there is also a true direct benefit to the patient besides this radiographic progression-free survival benefit. So in other words, do patient benefit clinically in terms of quality of life, in terms of time to pain deterioration and on top of safety as well? And what was we could show using the FACT-B questionnaire and the EQ-5D questionnaire for quality of life was that indeed time to deterioration in quality of life is improved or is delayed, if you will, with lutetium PSMA with a reduction in the risk of 40% for these men when they receive lutetium PSMA. Interestingly, also, different domains of quality of life are improved, including physical well-being, which I guess was expected because this is kind of direct a measure of the delay in symptoms patients may experience with this treatment when it's active, but also functional well-being, and emotional well-being is also improved. In parallel to that, patients receiving lutetium PSMA experienced a 30% reduction or improvement, if you will, in the time to deterioration in pain, which also is clinically super important. When we focused also on typical side effects that may impair negatively quality of life such as fatigue or anaemia, actually, grade 3 anaemia, we didn't see any difference between the two arms.

So I think we have a clearer package, if you will, for all the patients now regarding lutetium PSMA in this indication, we're clearly postponing imaging based progression, which is important from a registrational standpoint. Obviously, we are also postponing time to PSA progression, which is psychologically important to patients. They hate to see their PSA rising. But most importantly, we're postponing time to deterioration in quality of life and in pain deterioration, which is directly for the first time probably measuring clinical benefit, which I mean, to me, as a doctor, is so important to decide whether I should go or not for a given treatment in my practise. So this is where we are, and I'm happy to hear your opinions about those data, obviously.

Thank you so much for such a comprehensive outline and summary of the results. And it was a great presentation by the way, in the recent meetings we have had a chance to hear you. So it looks like great option for patients and especially many patients. As I said, Karim, do not want chemotherapy. Your real world use of chemotherapy with docetaxel remains around 30% in the US. So at least hoping that we will have another option for those patients who are very reluctant to pursue chemotherapy with docetaxel. They will have a chance or opportunity to have lutetium therapy before having to undergo chemotherapy. Thank you so much.

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