15th Congress of the European Hematology Association (EHA), 10—13 June, 2010, Barcelona

Interview with EHA Experts

Experts discuss treatment of elderly cancer patients

Participants:
GM: Professor Gordon McVie – European Institute of Oncology, Milan, Italy
RS: Professor Richard Sullivan – King’s College, London, UK
RR: Professor Reinhard Stauder – Innsbruck Medical University, Austria
MB: Professor Mario Bocccadoro – University of Torino, Italy
PF: Professor Pierre Fenaux – Paris XIII University, France

GM: Welcome to a round-table discussion about care of the elderly in haemato-oncology brought to you by ecancer.tv in Barcelona, coinciding with the European Haematology Association meeting. I’m Gordon McVie and I’m the managing editor of ecancer.tv and a senior consultant at the European Institute of Oncology in Milan. On that end, Richard.

RS: I’m Richard Sullivan, I’m a professor at King’s College, London with the King’s Health Partner Integrated Cancer Centre and I’m the lead on a joint initiative between King’s and the European Institute of Oncology around oncopolicy.

PF: Pierre Fenaux from Paris XIII University, clinical haematologist and I’m mostly involved in the treatment of myelodysplastic syndromes and acute myeloid leukaemia.

RR: Reinhard Stauder, haematologist from the Innsbruck Medical University, mainly involved in myelodysplastic syndromes and in geriatric oncology.

GM: My near neighbour, always the one, Mario.

MB: Mario Boccadoro from the University of Torino nearby Milano and my main interest is multiple myeloma in elderly people, of course.

GM: One or two oncopolicy backcloth points, Richard.

RS: Well the elderly and healthcare are probably the most critical issues facing developed countries today. And amazingly, despite the fact that nearly a third of the population across Europe is going to be aged over 65 by 2025, it’s still very low down the agenda for most governments and most of civil society; it’s still not recognised as a critical issue. So we have a rapidly aging population, we have major issues around the economics of how we’re going to pay for the care and there are also rapidly changing social situations for cancer survivors and for the elderly healthcare. Individuals are having less children and so there are less families around to look after elderly people and we’re actually seeing more and more people living alone and below the poverty line as well.

Amazingly the first guidelines coming out of, for instance, the USA weren’t until 1996, specifically aimed at cancer and the elderly. And in terms of social policy at federal level, recognising the elderly as a vulnerable specific population, in the same way that we recognise ethnicity these days, it’s simply totally absent. If you look around Europe these sorts of initiatives and policy recognitions don’t exist. All good policy should come from evidence rather than opinions and so one of those critical areas to look at is obviously what’s been going on, what are the views across Europe when it comes to ageism, concepts of ageism within management, within research, in MDS and AML? And the background to the literature really shows that ageism still does occur, that there are places where there is really very good practice and where actually people are applying what we know about oncology and the elderly very well, but there are still plenty of countries and centres and networks for which cancer care in the elderly, whether it’s an MDS, AML or breast cancer, whatever, is very poor. It’s still very, very poor.

There’s a whole slew of new targeted agents coming through which means you can deliver therapy now which is tolerated, even by the frailer elderly populations. And particularly when you look at the haem-onc community there seems to be, compared to the existing literature on solid cancers, a much greater recognition of the cancer in the elderly and the use of these new targeted agents to actually improve outcomes and treat a much wider population.

GM: So we want to make people listen, I think that’s probably the bottom line. The general issues that you’ve outlined, Reinhard?

RR: In newly diagnosed cancer, more than 50% are older than 70 years which means we are talking about the majority of our patients in the meantime. Treating the elderly is complex because you have to consider comorbidities, you have to consider cognition and these are the issues where haematologists start to consider, where they start to hesitate. Which means does the patient tolerate the chemotherapy, how should I consider the comorbidities, particularly heart insufficiency or renal insufficiency and does the patient understand what the plans are? Which means can I get an informed consent? These are two major points.

An important point is the individualised treatment which means you have to check the different dimensions – which are functional capacities, which is comorbidity, which is cognition, which is social support and additional starters.

GM: You’re mentioning the genomic situation surrounding the tumour, which is what we’ve been thinking about in terms of personalised medicine for the last two or three years since Gleevec, I suppose. Pierre, you’re saying that you’re interested in myelodysplastic syndrome?

PF: One third of the patients evolve to acute myeloid leukaemia but even if they don’t evolve to acute myeloid leukaemia, the prognosis is poor and it’s really a neoplastic disorder. Those patients predominate in the elderly so it’s a good example. They can be roughly divided into those who are considered low risk of progression to AML, where cytopenia and mainly anaemia are the issues. And those that are high risk with a short survival.

 When it comes to higher risk MDS they have a very short survival. Assessment of comorbidities is crucial and also the social environment because those patients are possibly fit for  transplant, will need some support. So here a geriatric assessment is really extremely important.

 Now we have the hypomethylating agents which improve survival and are less myelo-suppresive. What is very interesting is that they can be applied to very old patients and we regularly now apply them in patients even older than 80. Many, many people, even above the age of 80, can receive those drugs because they’re not too myelo-suppressive, they’re relatively well tolerated. A crucial aspect is to have those drugs administered as much as possible at home and tolerance is much better. And having enough cycles is crucial to improve survival.

GM: Because in the geriatric population there is an issue with oral medicine and compliance. This is taking the medicines to the patient in the community.

PF: Yes, and I think that’s crucial for the elderly. So in terms of compliance, of not wanting to stop the treatment and so therefore optimising the effect of such treatment.

MB: The therapeutic scenario in myelomas has totally changed in the last ten years because the chemo remains totally unchanged for at least thirty years and was the most famous Melphalan and Prednisone orally.

GM: Medical Research Council trial, 35 years ago, British Medical Journal.

MB: Then we had these new drugs and the survival of myeloma patients really changed. We moved from three years to five, six, and probably more. Younger patients, below the age of 60, their survival is really improved. If you look at the other patients according to the age, it’s not improved in the different decades. We have the same survival between 50 and 60, 60 and 70, 70 and 80. At that level in the younger population you see the curve that is going up because of the introduction of Thalidomide, Velcade, Lenalidomide, all these new drugs. On a population based analysis the elderly patient, at least in myeloma, I suspect, I don’t have the form approved, but I suspect that they are discriminated because they are not receiving the therapy. Of course it’s more difficult because the elderly people have comorbidities...

GM: It’s also more expensive and hospital budgets are restricted and you have to choose who gets the expensive drugs. Is that where the discrimination is or not?

MB: That point should be discussed because the usual treatment for an elderly patient is the following: I start with Melphalan and Prednisone.

GM: Not Bortezomib?

MB: Not the new drugs, not the new drug. I give the new drug when the patient will relapse. So the patient stays in remission a short period and then is treated with the new drug. So the cost at the end of the day or the end of the treatment is exactly the same but the quality of life is totally different and the remission period is totally different too.

 Of course we have to do a lot of work because if you are looking at the recent trials in the elderly patient, the rate of discontinuation is so high, it’s 40%. So it means that we need a protocol that is addressed to the elderly patient; we need an evaluation, a score.

GM: So you’re convinced that triple therapy works in older patients?

MB: Absolutely.

GM: Because that’s an important message. I mean one of the messages that I’ve been hearing is that it doesn’t seem to matter what your age is, you still deserve treatment. The treatment needs to be appropriate to your comorbidities and the aggressiveness of your disease, but you still deserve treatment and if you can put your patients in clinical trials you would do.

RR: So far in clinical trials mainly very fit patients are included. So inclusion criteria always starts or performance starts at zero or one. So the maturity of our patients…

MB: If you look at the trial with the new agents, Velcade and Lenalidomide, and you are analysing the patient according to the age, you see that there is an advantage of survival also in patients over 75. So there is a demonstration it is effective for the patient that is included in clinical trials, for the other not.

RR: We have to try to make the decision not based on their chronological age but on the biological age. You have to apply one score which assesses functional capacities. For cognition you have screening scores like mini mental status examination; for nutritional status you can evaluate body mass index or a more sophisticated one, measuring nutritional assessment. And for social support, that strongly depends on the socio-economic situation so it’s quite different depending on the background.

GM: Are there any biochemical tests or do you do ECGs? Matti Aapro told me that he does creatinine clearance and serum albumin, check kidney function, which is the most difficult to get out of a questionnaire, and albumin as a sort of catch-all for nutritional problems.

RR: Concerning the renal function, that addresses mainly the point of vulnerability. So which person is vulnerable, which person will not tolerate the chemotherapy.

MB: We have a lot of work to do to transfer that knowledge to the everyday practice.

GM: That’s what I’m getting at.

MB: It’s not used by the physician, a scale to define the biological age of the patient that you have in front. That’s the knowledge that is not still transferred to the cancer practice and that’s the reason why we have this Mediterranean group because that is raising awareness.

PF: Just also I’d be careful about scores. Of course they’re very useful but it also is common that the decision is also often taken talking with the patient. A good example would be acute myeloid leukaemia in the elderly, so we have the possibility of intensive chemotherapy or alternative treatments. Of course scores are going to give you an idea but it’s also talking to the patient. Coming in the room and seeing, ‘Wow, this patient’s too old,’ and of course also seeing the support of the family and so on. So you cannot rationalise everything, it has to be clinical judgment and it takes time.

GM: But obviously you need to think about the issue before you go in there and then you don’t want to make too subjective an analysis, and I think that may be what’s happening.

RS: If you were to go to the centres and networks and just ask them a simple question: have you considered policies of elderly in the cancer, have you got something, have you actually thought about this in your networks and centres? How many of them would answer in the affirmative? Very, very few. So even in a sense before we’re getting to developing the new scales and thinking about that, it’s bringing those individuals to the table and saying, “You need to think about elderly policies within your practice as a whole.” And this is the problem, we often talk about this very easy idea of transferability and we’re actually all working in quite different systems in terms of how we’re handling the patient flows etc. Having said that, there are some superb examples of best practice, we’ve just heard about this, about delivering treatment to the patient’s home. Now that doesn’t require different healthcare systems, that’s simply a very good idea which works which I’m sure, just on the back of an envelope you can work out, is much more cost effective than bringing the individual into hospital, particularly as in-patient.

GM: So do you think there should be somebody from geriatric medicine who is part of the multi-disciplinary team?

MB: Absolutely but we need a score that is possible to apply to the therapy that we want to deliver to the patient. So we need, really, a tight collaboration.

RR: We have to try to formulate guidelines or clinical recommendations and especially for the elderly which are in the intermediate group and in the vulnerable group. It helps you to set up the concept which means there are three groups of elderly patients. One group, those are the fit persons; we even make transplants in persons who are older than 70 years when they are fit. So they should get the treatment which is similar to younger persons. Then we have an intermediate group, the slow-goes, according to Balducci. They are maybe vulnerable so we have to make a kind of individualised, a kind of tailored treatment. And we have a third group, those are the frail, so we have best supportive care, we have palliative care is the best approach.

GM: I don’t agree with the third one, however we’ll come back to that in a minute. I think everybody should get it.

PF: What I’d like to say is that overall the new treatments we have, in most cases are relatively well tolerated.

GM: Absolutely, things have changed.

PF: So we know now how to increase the survival of myeloma with relatively non-toxic drugs, of myelodysplastic syndromes, of even lymphomas, especially with Rituximab. And now the problem of funding is going to come.

GM: Have you got any other final comment?

RR: I think the biological age is quite relevant. In the team geriatricians and oncologists should work together.

GM: Good idea.

RR: That’s perfect and we should try to establish recommendations in clinical trials, even for the elderly and even for those who are not fit.

GM: Thanks very much indeed. So I hope you’ve enjoyed watching these four seriously senior and authoritative experts talking about the issue of cancer in the elderly. We have got evidence that the haemato-oncologists are further on in recognising the issues related to the elderly than their colleagues who treat patients with breast cancer or lung cancer or renal cancer. The reason we’ve got to look at this issue much more carefully is prompted by the advent of less toxic, more targeted, more focussed drugs which will lead us, certainly me, to believe that we should not be withholding active medicines from any of our patients. And so we’re going to have to rethink the sorts of categorisation which we doctors have in our heads – low risk, medium risk, high risk. So the consensus is leading to a slightly more aggressive policy amongst the haemato-oncology community in terms of not discarding people on the basis of numerical age, focussing almost exclusively in future on biological age. We know that we have got a number of scores available to try and help with assessing patients who have got degrees of frailty, degrees of cognition, degrees of comorbidity, but a lot of them have been developed within the geriatric academic community and maybe have not percolated, filtered out, to the haemato-oncology practitioners and we think that maybe multi-disciplinary teams should include, alongside the haemato-oncologist and that coterie, also the geriatric expert for the future.

 I think there is a mixed uptake of elderly patients into clinical trials. I don’t think I’m going to be satisfied until everybody is offered a clinical trial, even if they’re very, very frail. We know the least about how to manage patients who are very, very frail and I think we need to have better teaching modules based on evidence-based guidelines which will help us deal with the assessment of the social aspects of an elderly person living alone with no grandchildren because there aren’t any grandchildren anymore because the birth rate is going down across Europe. We’ve tried to keep away from the cost issue here, we’re not focussing on economics, we’re not bashing governments for not putting enough money in, we’re just saying there is going to be a big cost coming down the line.

 Thank you again to the panel, Richard, Pierre, Reinhard and Mario. That was most stimulating, I have learned a great deal and I hope you did to. Bye bye from Barcelona.