Results and Lessons Learned from the Consensus Conference for Developing Countries - Fernando Maluf
February 2, 2020
Fernando Maluf, MD, Associate Director – Oncology Center - Beneficência Portuguesa, São Paulo Member of Steering Committee – Oncology Center – Albert Einstein Hospital, São Paulo, Brazil.
Charles J. Ryan, MD, the B.J. Kennedy Chair in Clinical Medical Oncology and Director of the Division of Hematology, Oncology and Transplantation at the University of Minnesota, Minneapolis, Minnesota, USA.
Charles Ryan: Hello from APCCC, 2019. We're in Basel, and I'm talking today with Fernando Maluf, old friend and colleague of mine from way back, where he is now the Associate Director of the Oncology Center of the Beneficência Portuguesa at the Oncology Center at Albert Einstein Hospital in São Paulo, and has presented what I think is a landmark achievement and something that will teach the world a lot. You recently completed and are analyzing the data from the first Prostate Cancer global Consensus Conference for Developing Countries (PCCCDC), and congratulations on that first of all. Second of all, tell us what your goal is with this data.
Fernando Maluf: It's a pleasure to talk to you, Chuck, an old friend. This was a big achievement that more than a hundred physicians from all over the world, particular for developing countries in Latin America and Africa and Middle East participated. The physicians included several specialties, include urologists, medical oncologists, radiation oncologists, pathologists and radiologists. And we pose a questionnaire of a multiple choice question of more than 350 questions evaluating from the screening towards diagnosis towards the treatment of localized, local advanced, and metastatic castration sensitive and resistant as well as biochemical recurrence sensitive or M0 CRPC. The best management that we can do and offer to patients in places that the resources were limited. So we come out from the ideal world in every scenario towards scenarios that poses severe limitations regarding infrastructures and treatment tools to help physicians decide on the day-by-day in every city, state or country, what's the best for their patients, whatever they had available at that point, at that moment.
Charles Ryan: So I think it's really important to point out, and I learned from you that in these countries that we'll call developing countries, there are many patients who are getting ideal world therapy or who are able to get... We were just having a conversation about full dose abiraterone versus lower dose. So tell us a little bit about what proportion of this population in the world, which I realize is many hundreds of millions of people, are not able to get what you might consider optimal therapy because of resource limitations. Do you know that number?
Fernando Maluf: Yeah. The number varies a little bit, but it's at least two thirds to three quarters of the world do not have the optimal care, not regarding only the drugs, but regarding the optimal radiation therapy, optimum diagnostic tools and optimal surgical centers that are able to operate patients, many like surgeons with experience in high patient volume. So with all that, I think it would leave less than 20 to 25% of the patients that really have been treated in places with all the full resources available. So a consensus like that is very useful, because as we did many different scenarios, we're going to try to provide guidance and recommendations that will fit to every city, state or country, in reality. Because there are some countries who do have the drugs available but the radiation is not ideal and vice versa. So there are many different scenarios and is very heterogeneous.
Charles Ryan: Is it the case that the physicians are relying on standard therapies from a previous era and in many cases are being creative, in that I saw in your data, for example, ketoconazole and DES are being used, corticosteroids are being used. These have been around forever. I use them a lot. I used to use them a lot, I should say. And these provide a substantial amount of benefit for a large number of patients, but in these countries, the physicians are, in a way, forced to be creative and use these therapies.
Fernando Maluf: Yeah, that's important question. That series of questions we pose to the panelists. When you do have only docetaxel available in the patient failed docetaxel and we don't have abi, enza, radium 223, cabazi or PARP inhibitor available. What do you do consider reasonable drugs to offer to your patients? So more than 75% of the panel voted as a positive sign to mitoxantrone, DES, ketoconazole and corticosteroids, corticosteroids alone, even bicalutamide on high doses. So for me it was fairly surprising because none of these drugs, again, has shown a benefit overall survival. But the community feel that when you don't have the other drugs available, they may offer some, maybe not survival benefit but may some quality of life benefit or some symptom improvement.
Charles Ryan: I think a lot about this question and ketoconazole is a drug I used to study, and did clinical trials with it. Ketoconazole is really interesting. There was not a survival benefit shown in the one Phase III study that was done with it. But if you look at patients who take ketoconazole and respond to it, they live a lot longer than patients who do not. So, if you will never have a randomized controlled trial that demonstrates survival, but that shouldn't dissuade or discourage physicians from picking it. And I think even DES has sort of a similar story. Whereas, if it's used in a patient and the patient's benefiting, that individual patient is likely to be living longer. So, congratulations on that. And we could talk a lot, but if viewers of this are interested in hearing more about these data, there will be, I'm sure, many publications to come from it, but if they're interested in looking at this data, has it been presented publicly in a forum where they can search it?
Fernando Maluf: Well not yet but we will. We are in the process of having seven papers that will be divided into screening, diagnosis, treatment of every disease state and probably this will come up in the next few months. Also, in this ASCO GU for 2020 we're preparing a consensus for bladder cancer as well as for kidney cancer.
Charles Ryan: Great.
Fernando Maluf: If colleagues from Latin American, Middle East, Africa, Eastern Europe or Asia would like to participate, I encourage them to send a mail to myself and then we can have these colleagues to be part of the consensus, part of the voting system. My mail is M-A-L-U-F, "maluf" followed by another "f" and a "c" as "church" @url.com.br.
Charles Ryan: We'll post it on the website.
Fernando Maluf: And I will be very happy to have other colleagues. So the many countries who participate, the more pure the responses and the answers will reflect what the leader opinions would like to recommend to the physicians from the community.
Charles Ryan: I think there are lessons for those of us in resource rich countries like the United States. There are things that we can learn from this process. You pointed out the use of orchiectomy for example. It's been said time and time again that we could save our healthcare system millions of dollars if we would recommend orchiectomy for our patients with CRPC who are going to be on lifelong androgen deprivation therapy. We've actually also shown that orchiectomy is more likely to be recommended for patients with worse financial situation and insurance, but that doesn't make sense because it's actually a cost savings or it could extend beyond that because it's such a cost savings. So I was interested to see your data, for example, that orchiectomy is recommended quite frequently and for good reason.
Fernando Maluf: Yeah, I mean orchiectomy as you mentioned, there are many studies, one of those that was published few years ago that showed that it saves at least 2000£ compared with AR agonist or antagonist and the longer the patient lives the saving is even more. The other important finding in our consensus is that when you do not have the standard dose of abi available, again recommend the standard dose for every patient to have access to, what option that were thought to be reasonable by their consensus was low dose abi with fatty food in their metastatic castration sensitive setting or in the castration-resistant setting, inpatients, asymptomatic or mildly symptomatic.
Again, it's an environment when you do not have the drugs or the food, drugs, or doses available. So again, we come up with very nice answers from the panel and one of those is that the docetaxel, is still keeps very strong as the therapy of choice in patients with M1 CRPC who do not have abi, enza, or other medications available, even in the novel high volume disease in the limited-resource setting, dependable with 74% of concordance, recommend doce and castration as the first treatment with castration, with orchiectomy, not with a AR agonist or antagonist.
Charles Ryan: Excellent. Well, congratulations on this achievement, and we look forward to reading... I look forward to reading your seven papers and hopefully, and probably more than that to come. So, Fernando Maluf thank you for joining us.
Fernando Maluf: Thank you, Chuck.