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Is the UK falling behind on lung cancer treatment?

Bristol-Myers Squibb developed the questions for this interview, but had no input into the responses or editorial write-up. BMS did check the interview for medical accuracy and compliance with relevant regulations.

Dr Mick Peake, Consultant and Senior Lecturer in Respiratory Medicine for the University Hospitals of Leicester, discusses how the UK compares to Europe in treating lung cancer, the innovations that are improving outcomes and the areas where change and investment is needed.

What is the current outlook for lung cancer patients in the UK? Is it in line with the best countries in Europe, as specified in NHS England’s Cancer Strategy?

“There's no doubt that the UK has been at the bottom of the pile in terms of the one-year survival and five-year survival. The main problem with lung cancer is that by the time they [patients] get to specialist care, the majority of patients have an advanced and, in a sense, incurable disease.

The patients that are at stages 3B and 4 are by far the biggest group, and these all have, essentially, an incurable disease. Some of them, though, will survive a long time. If we look at the very early stages of the disease, stage 1, you'd expect 75 per cent five-year survival - so if you picked up all lung cancers at stage 1, you'd probably increase five-year survival by 75 per cent; whereas if you go back to the mid-2000s, it was about six per cent in Britain. 

The percentage of people, who had stage 1 disease in England in 2014, was only 13 per cent, and only another eight per cent had stage 2. So the rest of them had stage 3 or 4. We don't have contemporaneous data on stage distribution for other parts of the world but we know that if you go back a few years in Scandinavia – particularly in Sweden and Norway – they were getting 18 per cent and 19 per cent stage 1. It’s still not fantastic, but it’s better than the UK.

So we've got a problem with late presentation. The problem I have now in Public Health England is in trying to increase public awareness, primary care awareness, in trying to get people to go to the doctor earlier.”

 

How can we improve survival rates for lung cancer? 

“The big problem at the moment is that 75 per cent plus have a stage 3 or 4 disease. A small percentage of those are curable with a combination of chemotherapy and radiotherapy. It may be that immunotherapy has a part to play in some of those when they recur. But the big problem with all the industry interests is in the stage 3B and 4, where we're giving essentially palliative chemotherapy.

We've gradually improved the impact of this palliative chemotherapy. For example, when we first looked at the median survival from diagnosis in 1995, it was just under three months. It's now about six to eight months, and in patients that are fit and well and get access to chemotherapy and a targeting agent and possibly immunotherapy, it's getting up to a median survival of 12-18 months.

But the number who get beyond two or three years is still very small. Our recent work on one-year survival by stage for England in 2014 showed that we had made big inroads into stage 1 and 2, and some in stage 3, but we haven't really made much impact on stage 4.”

 

You’ve worked with lung cancer patients for over 20 years. What have been the main breakthroughs in cancer care during this period?  

“Immunotherapy, for some people, has a remarkable effect. For small numbers, a lot of tumour disappears - sometimes completely, although not very often. When you look at the survival curves, which describe the proportion of patients alive over time, the curves fall; and in almost all clinical trials for advanced disease they eventually reach virtually zero, after two or three years.

What you see with immunotherapy is a plateau, from that declining curve, with around 20 per cent of patients with advanced disease, who have already had chemo and other treatments, living two or three years, and we don't know what the long-term survival of those people is. We know that a small number of them do really well. And we don't really know yet how to define who's going to respond well or not. 

The national lung cancer audit has been feeding back information to clinical teams for more than 20 years to show them how they perform. The biggest gap, in the 90s and early 2000s was in the proportion of people who had an operation. That's the treatment that's going to lead to cure, at the moment. If you can operate on an early-stage disease then you've got a high chance of long-term cure, and over the last 10 years, the number of people getting an operation has more than doubled. Our estimates for the five-year survival of 2013 patients put the five-year survival at 16 per cent.

I was saying earlier that we running at seven to eight per cent five-year survival in the 90s and early 2000s. So we appear to have made a major impact on five-year survival, going up to about 16 per cent. The proportion that are alive at a year has gone up from 22 per cent to about 39 per cent, so we've almost doubled the one-year survival. The bulk of that has been due to better services, better referral to specialists, more early diagnoses, and more people getting an operation. But we're still stuck with this large cohort of people we can't cure. 

The early trials were done with people who had already had one or two lines of chemotherapy and even in that group we were getting 20 per cent of people alive at two years, which is extraordinary. We'd never seen that in people who had advanced disease, who had already had first and sometimes second-line treatment, then going on to have another treatment.

It is a paradigm shift, I think, particularly in second-line or third-line treatments, when they've gone through conventional treatments. It's much less toxic than conventional chemotherapy in the second line context, because by the time people get to second or third-line chemotherapy, they are from a relatively elderly population.

Still, we don't yet know how to identify that 20 per cent. We don't know how long to keep the treatment on for, so you've got people who are doing really well, and two years on - what do you do? Do you stop the drug?”

 

Are sufficient resources being invested in lung cancer?

“The R&D costs for any new drug now are huge. You're talking about something like a billion dollars to develop an agent like this, with all the research and the safety efficacy. Companies have a relatively short period on the patent. I don't know if the actual production costs are as high.

The situation is that America can spend more, the market in America is hugely bigger, they're not controlled by NICE, and so in a way, the company can just say well, ignore the UK. It's too expensive to get it through, the numbers of patients who will get the drug in the population are small and interference from NICE means that the return on that market, if we reduce it in that market, then we'd have to reduce it in America, because we have to have parity. So they basically set the price based on the American market. But I don't know why they're so expensive to produce. 

The problem with NICE is that the way they assess cancer drugs is based on very old types of research. In the past, they would take chemotherapy A and chemotherapy B in first-line treatment, and they would look at the survival rates in a randomised control trial. And they would work out how much the drug costs, and what the survival benefit is. You've now got a situation where people may be getting three or four lines of treatment, and you can't make an A versus B comparison.

Clearly, this country cannot afford to give every lung cancer patient these drugs. You have to look at the bigger public health issue. I don't think we should just pump hundreds of millions extra into these drugs; you've got to look at the bigger picture. But I think there has to be a sensible and rational basis for how the government and industry come up with whether drugs are made available in England. 

I think we need a much more contemporary way of trying to work out what the health and economic benefits are. The current paradigm doesn't, in my view, fit the nature of these drugs. I think industry has a responsibility to work with the government. In virtually every area of cancer medicine, immunotherapy has the potential to play a part, and possibly a big part, once we identify which patients are going to respond. There needs to be some sort of high-level group, which brings industry, government and academic people together to think about how the UK can afford immunotherapy for the correct individuals.” 

ONCUK1601685-01

March 2017

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Leader: Trump's dangerous nation

From North Korea to Virginia, the US increasingly resembles a rogue state.

When Donald Trump was elected as US president, some optimistically suggested that the White House would have a civilising effect on the erratic tycoon. Under the influence of his more experienced colleagues, they argued, he would gradually absorb the norms of international diplomacy.

After seven months, these hopes have been exposed as delusional. On 8 August, he responded to North Korea’s increasing nuclear capabilities by threatening “fire and fury like the world has never seen”. Three days later, he casually floated possible military action against Venezuela. Finally, on 12 August, he responded to a white supremacist rally in Virginia by condemning violence on “many sides” (only criticising the far right specifically after two days of outrage).

Even by Mr Trump’s low standards, it was an embarrassing week. Rather than normalising the president, elected office has merely inflated his self-regard. The consequences for the US and the world could be momentous.

North Korea’s reported acquisition of a nuclear warhead small enough to fit on an intercontinental missile (and potentially reach the US) demanded a serious response. Mr Trump’s apocalyptic rhetoric was not it. His off-the-cuff remarks implied that the US could launch a pre-emptive strike against North Korea, leading various officials to “clarify” the US position. Kim Jong-un’s regime is rational enough to avoid a pre-emptive strike that would invite a devastating retaliation. However, there remains a risk that it misreads Mr Trump’s intentions and rushes to action.

Although the US should uphold the principle of nuclear deterrence, it must also, in good faith, pursue a diplomatic solution. The week before Mr Trump’s remarks, the US secretary of state, Rex Tillerson, rightly ruled out “regime change” and held out the possibility of “a dialogue”.

The North Korean regime is typically depicted as crazed, but its pursuit of nuclear weapons rests on rational foundations. The project is designed to guarantee its survival and to strengthen its bargaining hand. As such, it must be given incentives to pursue a different path.

Mr Trump’s bellicose language overshadowed the successful agreement of new UN sanctions against North Korea (targeting a third of its $3bn exports). Should these prove insufficient, the US should resume the six-party talks of the mid-2000s and even consider direct negotiations.

A failure of diplomacy could be fatal. In his recent book Destined for War, the Harvard historian Graham Allison warns that the US and China could fall prey to “Thucydides’s trap”. According to this rule, dating from the clash between Athens and Sparta, war typically results when a dominant power is challenged by an ascendent rival. North Korea, Mr Bew writes, could provide the spark for a new “great power conflict” between the US and China.

Nuclear standoffs require immense patience, resourcefulness and tact – all qualities in which Mr Trump is lacking. Though the thought likely never passed his mind, his threats to North Korea and Venezuela provide those countries with a new justification for internal repression.

Under Mr Trump’s leadership, the US is becoming an ever more fraught, polarised nation. It was no accident that the violent events in Charlottesville, Virginia, culminating in the death of the 32-year-old Heather Heyer, took place under his presidency. Mr Trump’s victory empowered every racist, misogynist and bigot in the land. It was doubtless this intimate connection that prevented him from immediately condemning the white supremacists. To denounce them is, in effect, to denounce himself.

The US hardly has an unblemished history. It has been guilty of reckless, immoral interventions in Vietnam, Latin America and Iraq. But never has it been led by a man so heedless of international and domestic norms. Those Republicans who enabled Mr Trump’s rise and preserve him in office must do so no longer. There is a heightened responsibility, too, on the US’s allies to challenge, rather than to indulge, the president. The Brexiteers have allowed dreams of a future US-UK trade deal to impair their morality.

Under Mr Trump, the US increasingly resembles a breed it once denounced: a rogue state. His former rival Hillary Clinton’s past warning that “a man you can bait with a tweet is not a man we can trust with nuclear weapons” now appears alarmingly prescient.

This article first appeared in the 17 August 2017 issue of the New Statesman, Trump goes nuclear