Dr Mary O’Brien, Head of the Lung Unit

The past ten years have seen a dramatic shift in the way we treat lung cancer patients. Thanks to the advances of immunotherapy, genetic sequencing, targeted therapies, new radiotherapy techniques and a programme of research investigating how best to combine all these treatment options, there’s palpable excitement at The Royal Marsden around the future of lung cancer treatment.

More than 46,000 people are diagnosed with lung cancer in the UK every year, making it the third most common type of cancer. But largely due to the fact that three-quarters of cases are diagnosed at a late stage, patients presenting with lung cancer have historically received a poor prognosis and treatments have been mostly palliative.

Dr Mary O’Brien, Head of the Lung Unit, says: “For early-stage lung cancer, surgery remains the main treatment option and can be curative. But lung cancer often doesn’t cause symptoms and isn’t diagnosed until it has spread, when surgery isn’t possible. In these cases, new targeted therapies, immunotherapy and new radiotherapy techniques are offering viable alternatives.”

In 2016, the immunotherapy drug pembrolizumab, and then in 2017, nivolumab – both of which harness the body’s own immune system to attack cancer cells – were approved for use on the NHS to treat lung cancer patients.

This is a landmark step and means a shift not only in survival but also in patients’ quality of life

Dr Jaishree Bhosle, Consultant Medical Oncologist

Dr Jaishree Bhosle, Consultant Medical Oncologist, says: “Research has shown that immunotherapy drugs increase the number of patients alive after three years two- or three-fold, depending on the type of lung cancer they have. This is a landmark step and means a shift not only in survival but also in patients’ quality of life.”

Combination treatments

The next stage of research is investigating how these immunotherapy drugs work in combination with other treatments. For example, the PEAR trial is looking at the use of radiotherapy in lung cancer in combination with pembrolizumab.

Dr Merina Ahmed, Consultant Clinical Oncologist, explains: “We’re trying to find out if different doses of radiotherapy in stage 4 lung cancer patients stimulate more of a response to immunotherapy. We are also doing this with the STILE trial in stage 1 cancer, hoping to improve cure rates even further and delay disease progression.”

The PACIFIC trial will study the use of chemotherapy and radiotherapy followed by immunotherapy, aiming for a cure for patients with locally advanced lung cancer.

Meanwhile, the HALT study, led by Dr Fiona McDonald, Consultant Clinical Oncologist, is investigating the role of stereotactic radiotherapy in patients with specific driver mutations who are being treated with targeted therapy.

She says: “Some of these patients develop limited progression of their disease in only one or two places while on such drugs. We are investigating whether adding stereotactic radiotherapy can delay disease progression and prolong the time that patients derive clinical benefit.”

We are investigating whether adding stereotactic radiotherapy can delay disease progression and prolong the time that patients derive clinical benefit

Dr Fiona McDonald, Consultant Clinical Oncologist

 

Although older people who have a history of smoking are still the most likely to develop lung cancer, over the past 10 years there has been an increase in younger non-smokers – particularly women – also being diagnosed.

Dr Sanjay Popat, Consultant Medical Oncologist, says: “We don’t yet know why this is – it could be a combination of genetic predisposition and environmental factors. But what we do know is that this type of patient is likely to have a genetic mutation that we can treat with a targeted drug.”

There are two known genetic mutations in lung cancer that are now routinely tested for: EGFR and ALK. Both of these can be treated with targeted molecular therapies.

Previously, patients with these genetic mutations would have gone through standard chemotherapy and had an average survival of a year. With these targeted therapies, combined with some chemotherapy, the average survival time is three to four years, with half of these patients alive beyond this and experiencing a better quality of life due to fewer side effects than standard chemotherapy alone. Patients are also spared the risky and invasive biopsies of the past, thanks to the introduction of blood tests to look for circulating tumour DNA.

Dr Sanjay Popat and Dr Fiona McDonald, who lead the PROMISE-meso and HALT studies respectively

Matching mutations

The Royal Marsden is a leading recruiter on the multi-site, multi-arm Matrix trial, involving patients with metastatic or locally advanced non-small-cell lung cancer.

Dr Popat says: “First, we take a sample of a patient’s tumour and look at which genetic mutations they have. We find out which ones might be simple ‘spelling mistakes’ that won’t cause any trouble and which ones are likely to drive “One patient with mesothelioma now has no evidence of the disease” tumour growth, and then we match them to one of eight new drugs.”

Dr Popat is also the Chief Investigator on the PROMISE-meso trial, which compares pembrolizumab with chemotherapy for patients with mesothelioma – the type of lung cancer caused by asbestos.

“In earlier Phase I and II trials with pembrolizumab, we’ve seen 61 per cent of mesothelioma patients showing evidence of tumour shrinkage,” he says. “I hesitate to use the word ‘cured’, but we have one patient with mesothelioma who now has no evidence of disease.”

One patient with mesothelioma now has no evidence of the disease

Dr Sanjay Popat, Consultant Medical Oncologist

Screening pilots

As well as kinder, more effective and less invasive treatments, early detection and rapid diagnosis are key to changing the face of lung cancer.

Dr O’Brien says: “Mature studies in the USA have proven that screening high-risk groups of people for lung cancer before they present with symptoms saves lives. Now in the UK, we’re running a number of screening pilots to see if we can emulate this.

“In our lead role in RM Partners, a cancer alliance of healthcare providers, we are funding a pilot for west London that is due to start this spring. We are also working with the NHS to speed up the patient pathway from diagnosis to treatment. When caught early, lung cancer is curable.”

Dr Popat concludes: “Ten years ago, a lung cancer diagnosis was bad news for patients. Now, for some, lung cancer can be managed as a chronic disease. We’re talking about surviving for longer and having a better quality of life.”