According to a media release, issued earlier today by Novartis, the company has provided preliminary data about the results of the international, multi-center, Phase III, randomized, VISION trial, which has been evaluating the efficacy and safety of lutetium-177 PSMA-617, a targeted radioligand therapy, in treatment of men with progressive, PSMA-positive, metastatic, castration-resistant prostate cancer (mCRPC).
We do not yet know the full details of the results of this trial. What we know at this time is the following:
- The VISION trial enrolled 831 a total of men with progressive, PSMA-positive mCRPC.
- These patient were treated with either
- Lutetium-177 PSMA-617 (at a dose of 7.4 GBq administered by IV infusion every 6 weeks for a maximum of six cycles) + investigator-chosen best standard of care (Arm A) or
- Investigator-chosen best standard of care alone
- The patients were randomized in a 2:1 ratio in favor of the investigational Arm A.
The trial is said to have met both of the two primary endpoints:
- Overall survival and
- Radiographic progression-free survival
Side effects observed in the VISION trial are said to have been “consistent with data reported in previous clinical studies”.
The company further claims that something of the order of 80 percent of men with advanced prostate cancer may be treatable with a drug of this type, which we take to mean that about 80 percent of men with advanced prostate cancer are positive for PSMA (prostate-specific membrane antigen.
Novartis expects that the full results of this trial “will be presented at an upcoming medical meeting” (maybe at the annual meeting of the American Society of Clinical Oncology later this year) and and that they will be “included in US and EU regulatory submissions”.
If these data prove to be acceptable to US- and EU-based regulatory authorities, one might see this drug approved for the treatment of men with progressive, PSMA-positive mCRPC some time in 2022.
WE should be clear that the patients enrolled into this trial had very late stage forms of prostate cancer. They had to have clear evidence of metastasis. They had to have progressed on standard forms of androgen deprivation therapy (ADT). They had to have received treatment with and progressed after at least one form of taxane-based chemotherapy. And they also had to have received treatment with and progressed after at least one form of androgen receptor blockade (e.g., a drug like abiraterone acetate or enzalutamide).
We should probably have limited expectations about the extent of any improvement in overall survival for men with such advanced disease. In the opinion of The “New” Prostate Cancer InfoLink any increase in overall survival is probably limited to 2 or 3 months.
What will, perhaps, be of much greater interest over time, is going to be the possible effect of giving a drug like lutetium-177 PSMA-617 much earlier in the course of care of men with metastatic prostate cancer, e.g., in combination with standard ADT at the time of onset of metastatic disease. We assume that Novartis is already looking at the possibility of conducting trials in men like this in the near future.
Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: castration-resistant, lutetium-177, mCRPC, metastatic, PSMA, PSMA-617 |
THE "NEW" PROSTATE CANCER INFOLINK 
Now we have two trials, VISON (700 patients) and TheraP (200 patients) that show that PRLT is better than the established alternative. Further, PRLT has limited serious side effects. Of course FDA and EMA wait to see the trials not only presented at meeting but published in relevant journals. The results of TheraP was presented last year and is still not published. Already many hundreds of patients have been reported for compassionate treatment of end-stage patients.
The gain in OS in the VISION trial was median only few months. But the perspect is the all established tretments of very advanced patients with mCRPClso had a limited gain in median overall survival of about 3 months, nevertheless called life saving.
Dear Finn:
So neither the FDA nor the EMA actually “wait” to see the data from trials reported at meetings or published in medical journals.
The manufacturer of any new drug is required to submit a highly detailed new drug application (NDA) in the USA or marketing authorization application (MAA) in the EU to regulatory authorities that includes all data relevant to the clinical use of the product in all investigational settings. Such an NDA or MAA includes detailed data on every individual patient use and not just a summary of the overall results from one or two clinical trials.
These applications commonly run to tens of thousands of pages of data and analysis. They are far more detailed than the published data and must meet far more rigorous criteria, specified beforehand by consultations between the company and the regulatory authorities. They are also entirely independent of any presentation at a meeting or publication in a medical journal. Indeed, the regulatory authorities can approve or not approve a new drug even if there have never been any presentations at meetings or results published in medical journals. Those presentations and publications are much more important to the key investigators who run the trials and to the drug manufacturers themselves than they are to any regulatory authority. These documents are also normally confidential because they may contain information that is covered by patents and other legal forms of privilege (including individual patient data that may be identifiable).
It is very important that you and others understand that reports at medical meetings and articles published in medical journals are simply summaries of data from clinical studies that may contain anywhere from a few (less than 100) to tens of thousands of patients. In contrast, in authorizing the use of any new drug (or any change in the use of any already approved drug), regulatory authorities like the FDA and the EMA have access to the data from every single use of the drug in every single patient treated in an investigational setting, and it is this set of information on which the prescribing information for the drug is developed and the drug is actually approved.
Actually, the Lu-177 PSMA treatment can also be useful for treating biochemical recurrence when the site of the recurrence is too risky for conventional treatment (e.g., a lymph node too close to an important nerve or organ, or a seminal vesicle that has already received the maximum dose). I asked Dr Nat Lenzo, an Australian nuclear medicine specialist, about this at a recent online talk, and he replied that in Australia they do this ‘all the time’ because the Lu-177 can treat the tumor without damaging nearby tissues. Unfortunately, it’s only a treatment, not a cure (though Dr Lenzo does say the node treatment is effective for a median of 33 months). I wish someone would start a trial on this application in the US.