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Value tops the agenda at ASCO cancer conference

Published on 30/06/14 at 08:01am
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The annual American Society of Clinical Oncology (ASCO) meeting has long been one of the most important events on the cancer research calendar. With academics and practitioners gathering from around the world to share new data and discuss best practice, the conference is often a platform for the announcement of major new treatment advances.

However, this year’s meeting was a little bit different. Although research into promising areas such as immunotherapy continues to make progress, there were no new data that really stole the show. Indeed, the four studies highlighted at the event’s plenary session – which are deemed the most important or practice-changing – were investigations of established drugs in new settings.

Instead, it was the much broader topic of value in healthcare provision – primarily from the US perspective – that prompted the most animated discussion. Looking at how the figures stack up, it would appear that, until now at least, value has not been a major consideration in American healthcare.

As illustrated by University of Pennsylvania medical professor Ezekiel Emanuel, who contributed to an ASCO panel discussion on value this year, the US is getting a pretty poor return on its investment. 

Last year, Emanuel notes, the country spent around $3 trillion on healthcare – a figure greater than the entire gross domestic product (GDP) of France, the world’s fifth largest economy – and yet Americans’ average life expectancy is shorter than dozens of other developed countries. Tellingly, plotting a chart of countries’ per capita healthcare spending versus life expectancy exposes the US as a notable outlier. 

More specifically in the context of US cancer care, expenditure is set to rise faster than GDP. This will lead to significant financial pressure on patients, according to the head of Cancer Policy and Public Health at King’s College London, Richard Sullivan.

“We cannot avoid doing the value work on this,” Sullivan says. “This is going to force the debate on how we are generally going to finance sustainable, equitable and affordable cancer care.”

Value: a complicated matter

Emanuel suggests that oncologists themselves have a part to play in squeezing value out of the system, by improving efficiency. Doctors need to cut down on unnecessary tests, he explains, and limit the prescription of expensive treatments when comparable, cheaper options are available. “Let’s be honest,” he says, “we as a community are not doing everything we can to lower cost.”

As Delaware-based oncologist and ASCO associate Greg Masters points out to Pharmafile though, cutting costs is just one of many factors to consider: “Value is also about benefit. I could give you a really cheap drug, but if it doesn’t do anything, that’s not good value. Value is trying to find the best drug at the most affordable price. 

“If a drug comes out that’s so expensive no one can pay for it, no matter how good it is, it wouldn’t really matter. There’s some threshold that no matter how good a treatment is, you can’t afford it. So that’s a balance you have to work out. There aren’t right and wrong answers, it’s a negotiation.”

For oncology healthcare consultant Diane Blum, who took part in the same ASCO discussion as Emanuel, value is subjective and dynamic. “Value of treatment and what it means to the patient is really influenced by the emotional response to diagnosis,” she suggests, drawing on examples of patients diagnosed with similar conditions who derive value from treatment in different ways. Some see it as a means of getting back to work, others view it as a way to gain more time with loved ones, while others still simply want to feel they are doing everything possible to beat their disease. 

Needless to say, the issue of value – particularly in cancer care – is emotive, and this was reflected in how heated some of the debates at ASCO became. At one panel discussion, an audience member accused the society of dwelling on algorithmic approaches to quantifying value, at the expense of considering patients’ experiences.

“This obsession with the cost of drugs,” the attendee said, “is an example of how this organisation is now colluding with the American health insurance [industry] to ration care to save money. I stand with the patients who don’t want to hear their doctor say ‘well, three months [extended survival] is too expensive, there’s nothing we can do about it’.”

ASCO president Clifford Hudis countered that his organisation was on the same side as those patients, and that his questioner was creating a ‘false dichotomy’ in which considering patients’ feelings and applying mathematics to the problem were completely opposing approaches.

He argued: “What we are developing is a framework for assessing value so that you can have an honest, open and transparent discussion with your doctor and make a choice that’s informed. We are the ones who are helping to define value and if you want to contribute to that, you are invited.”

Bringing value to the US

The question of value (and its close relation cost-effectiveness) has long been on the agenda in the UK. However, the general impression from speakers and audience members alike was that the US was unlikely to adopt a health technology assessment system similar to Britain’s National Institute for Health and Care Excellence (NICE). 

“We don’t want a threshold,” says Emanuel, continuing: “we’re not interested in how NICE goes about it, that isn’t the value proposition. Proportionality between the price and the benefits does seem a reasonable thing for everyone to want. That doesn’t mean you need a threshold like NICE has of £30,000 per quality adjusted life – those are two different notions.” 

As part of an effort to settle on some kind of consensus in the definition and measurement of value, the European Society for Medical Oncology (ESMO) is working on what it calls the ‘magnitude of clinical benefit scale’. ESMO board member Elisabeth de Vries was at ASCO to update attendees on the tool’s development.

As part of the proposed system, drugs newly approved by the European Medicines Agency will pass on to a dedicated ESMO team, which will analyse and mark them out of five. Drugs scaled at the highest levels of four and five will be highlighted to governments by the organisation as the ones most worthy of attention. 

Factors taken into consideration include overall survival, progression-free survival, hazard ratio, long-term survival, response rate, prognosis of the condition, quality of life and toxicity. “We do not take into account cost because of this heterogeneity across Europe,” explains de Vries – a move praised by several audience members at ASCO.

More details on the scale will be outlined at September’s ESMO conference in Madrid, but de Vries acknowledges that, particularly at this early stage, it will be ‘lively’ and subject to regular re-evaluation and amendment.

New immunotherapies on the horizon 

Beyond debates on wider healthcare issues, there was of course plenty of new cancer research to sift through at ASCO. This year saw the presentation of around 5,500 studies investigating a wide spectrum of treatments and clinical considerations.

As with last year’s event, the hottest topic was immunotherapy, and more specifically those treatments which target the programmed cell death 1 (PD-1) protein and its PD-L1 ligand. Major players such as Merck, Roche, AstraZeneca and Bristol-Myers Squibb have candidates in development – and they’re vying for pole position in the race to a market which FierceBiotech reports could be worth $25-35 billion per year.

Of these, Merck’s pembrolizumab (MK-3475) won particular plaudits from the ASCO board – both for its efficacy and side effects profile. Describing a study of the drug’s impact on patients with advanced melanoma, Steven O’Day of the organisation’s Cancer Communications Committee remarks that the low incidence of serious toxicity is ‘unheard of in this setting’.

According to lead researcher Antoni Ribas, O’Day is not overstating pembrolizumab’s relatively mild side effects: “This is one of the most benign therapies I’ve ever used in my clinic,” he says of the new treatment, which was found to have a one-year overall survival rate of 69 per cent. The Phase I study is ongoing. 

O’Day points out that one of the most promising trends in immunotherapy is that research is moving beyond its initial focus of skin cancer to other forms of the disease. “The revolution is here,” he declares, “and it’s bursting out of melanoma into solid tumours.” 

Merck is also investigating pembrolizumab in lung cancer, as well as head and neck cancer, with a Phase III trial in the former setting expected to start later this year. BMS is also expected to target lung cancer with a combination of two immuno-oncology drugs: the experimental nivolumab and the already-approved ipilimumab (Yervoy). Roche presented data at ASCO on its anti-PD-L1 candidate MPDL3280A in bladder cancer. And, back to lung cancer, AZ’s MEDI4736 progressed to Phase III this summer.

Interestingly, and perhaps as a result of heightened competition, MEDI4736 has been pushed directly from Phase I trials in this setting, begging the question: is it risky to rush the development of these treatments?

Masters thinks that’s a difficult question to answer: “We used to think that you always had to go from Phase I to II to III. But now – partly due to urgency – if we find something that really has a strong effect, even if it’s in a small group of patients, we want to figure out how to prove what the effect is.

“It’s like driving a Corvette. It’s good to have progress and it’s good to help patients, but there are dangers when you drive fast – you can’t see the obstacles as well. We all want to drive a Corvette, but we have to be careful – and some doctors and patients prefer to take a slower path. I think it’s important to do research in different ways.” 

PsiOxus: an SME making inroads

It isn’t just the major players who are in on the immunotherapy game, however. Plenty of small and medium enterprises were at ASCO showing off promising research of their own. One such firm, the Oxford-based PsiOxus, is investigating an oncolytic virus called enadenotucirev, which it hopes to move into Phase II trials this year.

With a combination of talimogene laherparepvec (T-vec, Amgen) and ipilimumab (Yervoy, Bristol-Myers Squibb) producing impressive results in melanoma at 2014’s ASCO, PsiOxus chief executive John Beadle tells Pharmafile that oncolytic viruses combined with checkpoint inhibitors are a key emerging trend in cancer immunotherapy.

“This fits with the now well-known analogy of ‘take your foot off the brake (checkpoint inhibitors) and put your foot on the accelerator’ (immune stimulation),” he explains. “Oncolytic vaccines are very well suited to the second half of this equation: they actively set up an immune response and rev up the immune system. Enadenotucirev is very well placed for this form of combination therapy.”

According to Beadle, the virus’s unique selling point is its effectiveness when delivered intravenously, rather than by direct injection into a tumour, which allows it to more effectively target cancers that have spread to other parts of the body. 

With research still at an early stage, PsiOxus will continue to test the virus and has plans to investigate its effectiveness against a number of different tumours: including cancers of the bowel, lung and bladder. The firm is also in the early stages of developing a virus encoded with antibodies for increased anti-cancer efficiency. 

Beadle explains: “Given the known delivery efficiency of enadenotucirev, this means that we can use this technology as a platform to simultaneously deliver combination antibodies to tumours: for example, it is possible to deliver the oncolytic virus, plus an anti-PD-1 and an anti-CTLA4 – i.e., the mantra of combination immunotherapies can be delivered in a single product.” 

Other trends at ASCO

In the frenzy to identify the next big breakthrough in cancer treatment, it is easy to forget that quality of life and caregiving are also major considerations for the thousands of oncologists attending ASCO. For Masters, bringing quality care to patients was a key theme this year. 

Revisiting his comparison of fast-paced research advances to driving a sports car, he says: “I think doctors can provide quality care without necessarily having the most up-to-date drug because a lot of the time, we learn that the most up-to-date drug isn’t the best treatment. If we can ensure that doctors are making treatment decisions for the right reasons, based on the right data, that’s more important than the speed of the Corvette.” 

A number of studies addressed quality of life issues: goserelin (Zoladex, AstraZeneca, off-patent) was found to help preserve fertility for breast cancer patients undergoing chemotherapy; in the same disease setting, zoledronic acid (Zometa, Novartis, off-patent) administered every three months elicited the same benefits as standard monthly treatment, leading to less toxicity and less cost; and discontinuing cholesterol-reducing statins in the last year of life was found to safely improve quality of life for terminally ill patients.

Another message highlighted over the course of ASCO, was that obesity is becoming an increasingly common cancer risk factor in the US. In his first press conference at the conference, Hudis drew attention to data which suggest it will soon overtake tobacco as the leading identifiable cancer predictor in the US. And during his president’s address, he branded obesity as the ‘tobacco of our generation’. 

The various issues raised at ASCO illustrate what a complicated disease area oncology is. Although immunotherapy remains the therapy focus of most interest, this year’s conference did not offer any answers as to which drug will lead the next wave of treatments in this field.

And the emphasis on value made it clear that, although innovation and scientific endeavour are critical in fighting cancer, ensuring that patients can actually benefit from those efforts is paramount. 

Hugh McCafferty

Pharmafile's flights and accommodation for the ASCO event were covered by Boehringer Ingelheim