Lung cancer cell. Credit: LRI EM Unit
Whether it’s exams, a COVID-19 test or a mid-treatment scan, waiting for results can be nerve-wracking. The anxiety. The unknowns. The implications for the future. The growing sense of anticipation as the day looms. Will it be good news, or bad?
This week, the whole of cancer research got some long-awaited results – and they’re a tentative thumbs-up. New data from the US National Cancer Institute (NCI), published in the New England Journal of Medicine, show the clearest signs yet that one of the most promising concepts in modern cancer medicine – targeted therapy – seems to be having an impact on one of the hardest cancers to treat: lung cancer.
Lung cancer is the biggest cancer killer, claiming an estimated 1.76m lives each year around the globe. Thankfully, in many countries, the rate of people dying from the disease in the population has been gradually falling for several years. And although there have been some big changes in how the disease is diagnosed and treated over this time, the main thing driving the drop is the decline in smoking rates across the developed world, meaning fewer people are getting lung cancer.
This is of course, extremely good news. But the huge influence smoking has on cancer rates has made it harder to unpick any underlying impact of treatment changes. A large US analysis looked at this back in January, and appeared to show a big drop in death rates from all cancers – which was initially lauded as proof that treatment was improving. But a closer look at the data revealed that other factors were at play – including the drop in smoking.
The question of whether specific changes in treatment lead to population-level improvements in cancer outcomes is, of course, much more than an academic one. Over the decades, billions of pounds, dollars and euros have been invested in understanding cancer and developing new treatments. In the case of lung cancer, this has led to a whole slew of new therapies being approved in the last 5-10 years, and making their way into routine use – including in the UK.
Most prominent of these are the so-called ‘targeted’ therapies, designed to treat patients whose cancers are caused by particular DNA errors. After being proven effective in clinical trials, these drugs began to enter routine use in the early 2010s.
As a result, many researchers and organisations – including Cancer Research UK – have been keeping a keen eye on national and international cancer trends, looking for signs that this collective effort is having the ‘big picture’ impact that the positive trial results suggested they should.
A not inconsiderable number of fingers have been crossed.
Hitting the target?
We’ve written before about the promise and challenges of targeted therapies – also referred to as ‘personalised’ or ‘precision’ medicines. Unlike conventional chemo drugs, they’re designed to interfere with specific processes within cancer cells, with the aim of more precisely targeting the disease.
Thanks to the help of our supporters, we’ve been able to play a key role in accelerating the development of these drugs. Our researchers have been at the forefront of tracking down molecular faults in cancer cells, and finding ways to target them. We’ve worked closely with pharma companies to help test experimental therapies, to bring those that are safe and effective to patients as swiftly as possible. And we’ve worked closely with the NHS, to ensure the necessary testing is available to patients, –and regulators, to make sure their approval happens smoothly.
And yet, despite the hope and promise, lingering doubts remain.
In trial settings, these drugs can offer only modest benefits – months rather than years. They are extremely expensive. So too is the testing infrastructure needed to use them effectively, and only about 1 in 5 patients has a relevant marker suggesting the drugs will work. As with chemotherapy, tumours can develop resistance to them. They cause side-effects – different side-effects to chemo for sure but, for many patients, no less debilitating. Many commentators have written about the ‘hype’ around these drugs, and wondered whether they might be a false, expensive dawn in the quest to beat cancer.
The new analysis from the NCI begins to suggest otherwise.
Promising new data
This week’s new analysis draws on data from lung cancer patients diagnosed in the US between 2006 and 2016, and relies on the fact that the disease exists in several distinct forms. Two thirds are what’s known as ‘non small cell’ lung cancers, while just over a tenth are termed ‘small cell’ lung cancers. Both can be caused by smoking, but – crucially – targeted drugs have only been widely introduced for the former.
These facts allowed the NCI’s researchers to compare lung cancer incidence and mortality for both forms, using data from the organisation’s massive national Surveillance, Epidemiology, and End Results (SEER) cancer registry. Any difference in trends, the researchers reasoned, would likely to be due to factors like treatment changes, rather than other ‘bigger picture’ factors like smoking or improved diagnosis.
As expected, the analysis revealed that from 2006 mortality rates declined for both forms. But from 2013, the researchers spotted a big increase in the downward trend for patients with non-small cell lung cancer, which wasn’t apparent for those with small cell cancers.
2013, of course, is when targeted therapies began to be used for non small cell lung cancer.
The drop in mortality seemed to double, from 3% a year, to 6% a year. And when the researchers looked at 2-year survival data (the proportion of patients still alive two years after their diagnosis) this appeared to rise from about a quarter to over a third.
That’s a big improvement, for a notoriously hard-to-treat cancer. And it’s wonderful news.
But there are a few caveats. It’s not absolute ‘smoking gun’ proof that targeted therapies are behind the improvement – the SEER database doesn’t record which treatments a patient received, making the link an indirect one. Over the same time, there have also been incremental improvements in chemotherapy, radiotherapy and surgery. But many of these applied to both diseases, and the researchers were able to rule out many other factors, such as improvements in diagnosis leading to more cancers being diagnosed earlier, making their case extremely compelling.
No room for complacency
Despite this welcome news – in a type of cancer where progress has historically been slow – the study also highlights how much further we have to go to keep improving things for all patients, including those with non small cell lung cancers.
These drugs may be good – but they’re not good enough: they’re not cures, and they’re not suitable for everyone. Cancer, and lung cancer in particular, is a complex, rapidly evolving disease – so finding suitable drugs for more types (and subtypes) of cancer is going to be a long slog. And, as our National Lung Matrix Trial results suggested last month, non small cell lung cancer’s ‘low-hanging fruit’ may already have been plucked.
It will also be important to make sure that any new drugs are made available, and affordable, to all patients who need them. And just focusing on drugs certainly won’t be enough. Lung cancer can be curable in its early stages – we urgently need better ways to diagnose the disease early, to give people the best chance of long-term survival.
We know how much work is still to do, despite this week’s good news.
But there is reason to be incredibly proud of your support for us. Those key lung cancer drugs introduced in 2013 are designed to target a molecule known as the epidermal growth factor receptor, or EGFR. This crucial molecule was discovered in the 1980s, by researchers at our London Research Institute – now part of the Francis Crick Institute.
None of this week’s good news would have been possible without that breakthrough.
And today, hundreds of researchers at the Crick, and around the country, are continuing to make discoveries that, we hope, will keep improving things for all people affected by cancer.
And with COVID-19 having had such a big impact on charities like ours, your support has never been more valuable, nor more appreciated.
Henry Scowcroft is Cancer Research UK’s communications strategy lead