Hello, we’re here at ASCO 2017. I’m Will Davies, the ecancer medical reporter and we’re joined by our fantastic roving contributor Bishal Gyawali, thanks for joining us today.
It’s my pleasure, thank you.
You are probably famed for your contributions to our website with your hopes and hypes of ASCO and we’ll hear more about those later but what would you say have been some of the standout presentations, posters you’ve come across so far?
There have been a couple of very important presentations this ASCO and a couple of presentations that I’m very, very happy about. Because, unlike other big meetings, this year’s ASCO featured a couple of presentations that were really impactful for the global cancer population and a couple of studies that actually mattered to people and society instead of just hyping immunotherapies or other expensive drugs that easily happen in most of the meetings. So this time the ASCO meeting was a bit different from other meetings in the sense that there are a lot of things to be actually excited about.
Maybe it’s just the years of all those small gains finally paying off with some of the gains that we’re seeing now, everything coming together.
Yes, it could be. It could be like a change in culture because there are a lot of people who are voicing things against what’s going on in oncology, the recent trends of hijacking of evidence-based medicine for the profit of certain industry or for supporting the bias of certain groups of people or organisations. So now a lot of people are starting to think about what actually matters to patients and how actually we can address the issues of the patients. So I have seen a very positive change and I feel more optimistic now than ever.
One of the main send outs that I’ve seen regarding quality of life was one of the news pieces from Friday looking at a web-based intervention where patients could feed back their symptoms, their experience to an ongoing medical record and that was having benefits to quality of life, benefits to even survival second only to one or two drugs being discussed at this year’s conference.
Yes, that’s right, that was the second plenary presented by Eton (?). That is a very important paper and it’s interesting that last year in ASCO we had one not exactly the same but a similar type of study done in lung cancer patients and that showed a significant survival benefit of seven months with the use of web-based applications. This year we have got a plenary presentation of a patient-reported outcome study in which they saw that the use of patient-reported outcomes showed not only benefit in quality of life but also it improved survival by five months which is more than the survival benefit we have seen with other drugs. That is very important in a number of ways. Number one, that it got plenary means a big thing so that ASCO is giving importance to this type of studies. Number two, that we are seeing survival benefit with patient-reported outcomes means until now we have been talking about [?? 3:03] but what I wrote in my blog last month was patients are their own best doctors, patients know their symptoms much better than we do. With routine follow-up the problem is the patient, even if he or she has a number of symptoms they usually wait until they come to the outpatient clinic, until the scheduled date for the clinic. But what this study and other similar studies have shown that when patients with the help of a tool when they input their symptoms and they provide feedback to the healthcare team, like live feedback, when they have symptoms they fill in the symptoms and depending on that the healthcare team responds to that so they don’t need to wait for their outpatient appointment, they get better care, faster care. The same study showed that the duration of being on chemotherapy was longer in such patients and they could have a better quality of life. So these are the things that actually matter to patients and no wonder it led to an overall survival benefit. There were a couple of hypotheses discussing why it led to a survival benefit as well because we would expect only a quality of life benefit. But I’m not surprised because patients are the best doctors, we are there just to help them.
It turns out when you listen to patients and then treat them then they do well, who saw that coming?
Yes, a complete surprise.
Another grand surprise from a trio of presentations given on Friday looking at psychological interventions for patients on diagnosis, dealing with the fear of relapse and also advanced cancer patients finding that, again, if you listen to your patients and respond to their concerns with either online, face-to-face or blended cognitive behavioural therapy, like this STORM trial that was published last month in JCO, then, yes, people tend to do better.
Yes, that was a very interesting study again. That was in breast cancer, the fear of recurrence decreased significantly with the use of an intervention, they called it the Conquer Fear intervention. That’s a very proper name. Yes, no wonder, we are going back to basics and going to back to basics is the most important thing. We should not forget our fundamental principle in being a physician - we are there to take care of patients and how do we take care of patients? We listen to them, we listen to their concerns and we try to address these concerns. So that’s what we are going back to.
And another theme, moving away from treating smart was also treating less. We’ve had some significant trials about treatment reduction coming out of this year’s conference as well.
Yes, that’s why I was so happy about this year’s ASCO because one of those studies got plenary again, that was three months of adjuvant oxaliplatin based chemotherapy versus six months of the same treatment in colorectal cancer patients. But there are a little bit of issues that I want to discuss on that study: it did not reach the statistical margin of non-inferiority. And now the interesting thing is we have seen a lot of poor quality studies of new drugs that are testing non-inferiority against the standard of care and they put a margin of 25% as an acceptable margin of non-inferiority and they sell their product as being non-inferior so this would be appropriate. But now we are testing something that is of real benefit – three months of oxaliplatin versus six months of oxaliplatin based chemotherapy. Oxaliplatin is a really toxic drug in terms of neurotoxicity and we are talking about adjuvant chemotherapy in which patients don’t have the disease so we are giving adjuvant chemotherapy in the hope of preventing recurrence. In that case lesser is better; the less chemotherapy you give the better it is, provided it does not have worse outcomes. What we saw in this study was that the actual difference, if you see the actual difference in three year disease free survival, it was 1%. So that, for me, is non-inferior. If you see the statistical margin the margin for non-inferiority was 1.12, the upper margin of non-inferior [?? 7:33] confidence interval but in this study it happened to be 1.15. So it is a little bit higher than the margin but the general conclusion in the oncological community was non-inferiority cannot be established so six months would be the standard of care. I don’t agree with that, I agree with the conclusion made by the IDEA team, the team that did the study, and they made a very nice conclusion that if it’s a low risk disease, of course you need a patient sub-group analysis, but if it’s a low risk disease then three months is enough and if it’s a high risk disease then 3-6 months, you need to talk with the patient depending on his priorities, whether he or she wants to avoid neurotoxicity or not. If there is a patient who really wants to avoid neurotoxicity then I would encourage him to three months of therapy because the absolute difference you see was nearly only 1% in three years disease free survival. We have been bending some of the statistics for approving newer targeted drugs and immunotherapies and here we are becoming like a very puritan statistician and we are saying that this little margin does not prove…
In fact we heard very similar results only earlier today from Professor Pierfranco Conte who was talking about the ShortHER trial looking at a very abbreviated course of trastuzumab with chemotherapy for breast cancer compared to the full year. Again only just falling short of non-inferiority and if you discount the high risk patients with four positive nodes then it’s equivalent and you get equal outcomes for a much more endurable and durable response for patients with so much reduction in terms of side effects and cost. If you put that together with possible approvals for Herceptin biosimilars you end up with a cheap drug for less time for equivalent outcomes. This could be the start of something big.
Exactly. This was a very important study that got overshadowed by its loss of statistical significance but it is very clinically meaningful in the sense that we have a lot of patients in low and middle income countries who are unable to afford trastuzumab and they are likely unable to afford trastuzumab biosimilars either because biosimilars, the price will be lower than Herceptin but still it’s not generic, it’s a biosimilar, so you can’t expect a 50-60% reduction in price, it’s still going to be substantially expensive for people living in Africa, in Nepal, in India. So this study is important because it shows that three months of trastuzumab therapy it could not reach statistical significance but the difference was not substantial. On the positive side there was low cadiotoxicity and so what we are talking about is whether using three months of trastuzumab, does it provide the same outcome as one year of trastuzumab. We can’t say for sure because of the statistical thing but does it change practice in low and middle income countries or people in high income countries who can’t afford the full course or people in high income countries who have cardiotoxicity? Yes it does, so when I practice in Nepal I’ll be very happy to recommend nine weeks of trastuzumab because there are a lot of people who can afford only nine weeks because that’s a limited amount of money so you might sell some of your property and afford nine weeks of trastuzumab. But if I tell them that you need to continue for 52 weeks then they will not be able to do that.
And you can imagine not only the knock-on effect to quality of life but also patient outlook there to be told, ‘You cannot afford this drug,’ then it will plummet immediately I can imagine.
Yes. Whenever we talk about unaffordability of drugs it’s not only the drug that the patient is deprived of, the patient is also deprived of hope, the patient is deprived of confidence. We have seen that psychological interventions, patient reported outcomes, these things actually matter in survival too. So when we are giving hope we are enriching the patient with not only the drug but he has a future to look onto. This type of studies that we are having here, there is one more study about non-inferiority of 18 months of androgen deprivation therapy compared to 36 months in prostate cancer.
Yes, I spoke with Professor Abdenour Nabid yesterday. I was about to just bring that up as a way of segueing further onto prostate cancer. Yes, half the course for equivalent outcomes across 630 items, there’s no reason to do much more it seems.
Yes, we have these three important non-inferiority studies in this ASCO meeting that asked actually very important and pertinent questions. We have seen that non-inferiority, a shorter duration of therapy does not lead to worse outcomes. This means it opens up a new avenue for this type of studies across all tumour types, across many cancers. I had written a paper in the Journal of Global Oncology about bevacizumab in cervical cancer - most of the drugs, especially in the metastatic setting, the trend is to use the drugs until progression. So you keep on using the drug until the patient dies or until the disease progresses. Now people are talking about using some of the drugs beyond progression. But I think the paradigm has to shift and we need to test whether a limited course is enough. If a limited course is enough then you are only giving toxicities and high expenses to the society and to the patient. So because of these three studies we need to have a completely different view of treatment duration in cancer and we need to be testing shorter durations of therapy. For example, ipilimumab in melanoma adjuvant setting – ipilimumab for metastatic melanoma is used for four courses only but in the adjuvant setting we have one year or three years of trials. So that didn’t make any sense to me and I talked about it in last year’s ESMO video with ecancer. Instead of trying to take the longer durations of therapy maybe we should come back and see whether shorter durations of therapy are enough.
Instead of challenging patients to endure their therapy give them time to recover.
Yes, that’s very important because in oncology we have something called a concept of chemo holiday. Not exactly chemo but now we have targeted drugs and immune therapies too but the chemo holiday concept is very important for patients because whenever you are giving a drug to the patient you are asking the patient to leave his job for that day or for the duration of side effects and he has to come to the clinic and he will be using a lot of health services and the cost associated with health services, not only the cost associated with the drug. Days off work and a carer might have to come with him or her and the toxicities and management of toxicities.
So looking at costs beyond just the price on the bottle there.
I suppose we can’t talk about ASCO 2017 without raising more prostate cancer news, the STAMPEDE and LATITUDE trials which have captured a lot of people’s attention.
Yes, these are very, very interesting studies and both of them were published in The New England Journal. This could be a practice changing study because there was a very nice increase in overall survival, it was a pretty good increase. But it has to be put into context with another publication from the STAMPEDE trial itself a couple of years ago and that was docetaxel up front. So now we have two options up front compared to androgen deprivation therapy alone: androgen deprivation therapy plus abiraterone also increased overall survival and androgen deprivation plus docetaxel has also increased overall survival. So the key question is what should we use up front or someone is even talking about whether we should combine both and use a triple therapy of androgen deprivation plus abiraterone acetate plus docetaxel. Of course we don’t have data for those things yet and we need future trials. We need trials to compare androgen deprivation plus abiraterone versus androgen deprivation plus docetaxel head to head and maybe that could give us some idea. But for now when we need to make a decision in the clinic whether to use docetaxel plus androgen deprivation or abiraterone acetate plus androgen deprivation it all depends on patients preferences because the side effects are different and quality of life is different; docetaxel is a chemo, abiraterone has a relatively low side effect. But we should consider financial toxicity too – abiraterone is very expensive compared to docetaxel. Docetaxel is an old chemo so it’s not that expensive. Of course it has other toxicities, the docetaxel has other toxicities that abiraterone doesn’t have but financial toxicity is an important consideration in this case. Abiraterone was given for two years in the STAMPEDE trial so two years of abiraterone is a long duration for the patient in the sense he has to maintain the adherence to the therapy and he has to come for continuous follow-up but docetaxel is given for a limited number of cycles. So the things that we already discussed about keeping patients on a long duration of therapy or giving him a chance of chemo holiday for a long time. So I would personally prefer docetaxel up front rather than abiraterone acetate for financial toxicity and duration of therapy reasons but I would also understand if someone would like to take abiraterone up front instead of docetaxel because the side effects are different. This should depend on patient preference. One more thing is with docetaxel we saw that it is especially very effective in cases of high volume disease but abiraterone seems to be good irrespective of volume of disease. So that could also come into consideration but we need definitive trials.
There was a comment from Professor Schilsky during one of the press sessions earlier today that by comparison to some of the advances we’re seeing all the news that was shaking everyone’s world a few years ago looking at PD-1, PD-L1, CTLA-4 seems old by comparison but there are still lots of trials still coming out, lots of new patient groups emerging, lots of new combinations. We’ve heard of PD-1, CTLA-4, nivolumab and ipilimumab being used together for melanoma, for sarcoma, for all kinds of indications, all kinds of diseases. Have any of those been on your radar, anything you’d like to see more of?
Yes but personally I haven’t had a chance to go through all those.
There is a lot.
There is a lot going on in ASCO and my preference was to check the sessions where there were very significant benefits for patients instead of some hopeful treatments for the future. But if they lead to good patient outcomes then we’ll see
Mostly they seem to lead to having twice as much toxicity for being in with a shot of being one in six patients who respond which is not maybe the best kind of odds but they’re the odds that people will have to take if they’re going to progress with some of these medications getting towards the better outcomes that we can hope for.
Yes, it’s always a trade off with benefit versus toxicity unless there comes the role of biomarkers, unless we can have a good biomarker to identify patients who actually benefit then the toxicity benefit equation changes completely. So we know that this patient is going to benefit so we can ask that patient or the patient himself will be ready to accept a higher level of toxicity because he knows that he has a higher chance of benefit. But right now, as you said, one in six patients, we don’t know who is going to benefit and who is going to face only toxicities without going to benefit at all. So that is why it’s difficult so I think we need to focus on investigating proper biomarkers especially for these expensive and toxic agents because our first principle is first do no harm, that’s the Hippocratic principle and we have all taken the Hippocratic oath. So if we follow that principle of first do no harm we need to know whether we are going to harm the patient more or whether we are going to benefit the patient more.
I’ve only just remembered, how could we talk about dose reduction and financial toxicity without looking at the poster that… I can’t remember how many tweets and retweets it’s got on social media now but a saving of almost a billion dollars to the US healthcare system by just reducing the dose of PD-1 therapy.
I know that very well because the first author is my very good friend and colleague, Daniel Goldstein. So Dan did a very smart study. What’s happening with pembrolizumab is pembrolizumab has been approved at a dose of 2mg/kg body weight or sometimes 10mg/kg body weight in trials but right now they are starting to change it to a fixed dose of 200mg for everyone, a flat dose of 200mg. The problem that Dan saw with this was there is no difference in efficacy so instead of weight based dosing of mg/kg they are trying to give a fixed dose. Of course it’s easy to promote because it’s easy to remember for everyone, no need for calculations, everyone gets 200mg. But, for example, you have a 60kg man and if you give 2mg/kg it’s only 120mg but they want us to give 200mg to everyone so that will lead to more consumption of pembrolizumab. So Dan calculated using positive impact analysis that in lung cancer alone this would lead to 0.8 billion of extra money if you use a fixed dose instead of a weight based dose. This, Dan tells, is a personalised therapy, this is a personalised therapy based on your weight. So this was a very smart study and it deserved all those retweets and likes on Twitter and social media because these are small things that make a big difference. So Daniel Goldstein with one stroke, this was a billion dollar stroke, this was a billion dollar paper.
So we’ve been speaking with some of the key leaders, some of the presenters that we’ve had but I’m sure you’ve met so many more people here at ASCO. What else has caught your attention that maybe we haven’t had the chance to cover so far?
One more paper that was presented by, again, my friend, my very good friend, which I would like to discuss is the paper that showed that pregnancy does not increase the risk of recurrence of breast cancer
Matteo Lambertini, yes.
Yes, Matteo Lambertini, he is a very good friend from Italy now working in Belgium. We keep on talking about RCT evidence versus real world evidence and this was real world evidence. Real world evidence has its place for studies like this; real world evidence is not a good strategy to approve drugs, to say that this drug is beneficial. But for such type of clinical questions that are actually important and that you cannot do in RCT, this type of real world evidence will mean a lot. So this study will mean a lot to so many breast cancer patients that are young and that are contemplating pregnancy but who are afraid to be pregnant because of the fear of recurrence. So with this study we can tell them, ‘Look at this study, you don’t need to fear about it.’ But we should not be very complacent because this study looked only about breast cancer recurrence, it did not look whether the pregnancy outcomes were better or not or whether complications…
They did note complications including spontaneous miscarriage were increased but that recurrence and relapse for breast cancer as a disease, that at least showed no change in terms of pregnancy.
Yes, that was a very important study and I was very happy to see that. As I told you, this ASCO has given so many studies that are immediately applicable to so many patients. So this study is immediately applicable, tomorrow you can tell your patient that you don’t need to worry about being pregnant because the outcomes will not change. I’m always excited when you get some news from these big meetings that you can immediately use tomorrow in the clinic, so this is one study that you can use immediately tomorrow in the clinic. Pembrolizumab dose you can use immediately tomorrow in the clinic. Three months, six months of oxaliplatin therapy it doesn’t need any approval, you can use it immediately tomorrow in the clinic. Patient reported outcomes study you can use tomorrow, you need a set-up for that. That is what I discuss in social media with other friends that this patient reported outcomes study is so important – five months of survival benefit. But every institution doesn’t have the set-up so we need a set-up, so for that are the payers going to fund it? Are the payers going to pay for it? They happily pay for nivolumab and pembrolizumab but are they going to pay for building the system, having patient reported outcomes being sent to the clinician by the patient in real time? Who is going to fund for that?
If Daniel Goldstein has just saved them $800 million I’m sure they can take some of that and put it towards actual clinically proven benefit now.
Yes, I hope they do so, that’s why I keep on telling we need a centre for sense in oncology. We need sense in oncology; common sense is the most uncommon thing
Between common sense and listening to patients I think we’ve got right down to what it means to actually care for cancer patients. That was the main theme of this year - managing cancer care with you.
Exactly. Without you there is no cancer care, you should be involved in the cancer care. The patient should be involved in cancer care because we are taking care of you and we can’t take proper care of you without listening to you and without making plans with you together for what is important to you, what matters to you. This is what personalised therapy is, every patient is different, every patient has different hopes, has different expectations from treatment, has different thresholds of financial affordability, has different thresholds of toxicity tolerance. So making a difference in cancer care with you, that’s a very, very proper theme
Is there anything else you’d like to add?
I’d like to thank ecancer and I’d like to thank all the patients and I’d like to thank all my readers and followers on my blog. My blog has recently reached one year and it’s all possible because of all your help and your support. I hope we keep on walking this journey together.
Thanks so much for joining us today and we look forward to hearing more from you very soon.
Thank you very much, it has been a pleasure.