An integrated approach combining prevention, interception and treatment to tackle lung cancer

We aim to eliminate cancer,” says oncologist Peter Lebowitz. “We talk about it a lot; it’s part of who we are. It's not going to be tomorrow or next week, but we will get there.”

Such sentiments might seem like wild optimism. However, Lebowitz is global oncology therapeutic area head at the Janssen Pharmaceutical Companies of Johnson & Johnson, and he and his colleagues have a comprehensive, multi-pronged approach to achieving their goal. The strategy is based on combining prevention, interception and treatment, and as a company working in all of these areas, Johnson & Johnson is in an ideal position to take a multi-modality approach to the problem.

They are starting at the top, with the biggest killer of all the cancers. Lung cancer is particularly deadly because it is at an advanced stage in most patients when it is diagnosed. It is also more aggressive and harder to treat than most other cancers. Worldwide, almost 1.8 million people died of lung cancer in 2018 - more than the second (colorectal) and third (stomach) most deadly cancers combined.

This immense need led Johnson & Johnson to launch the Lung Cancer Initiative (LCI) in 2018. Its aim is to work with innovative collaborators worldwide to discover better ways to prevent, intercept and treat early stage lung cancer by bringing together the expertise and science of all three sectors within Johnson & Johnson, which includes medical devices, consumer products and pharmaceuticals.

“Most cancers, including lung cancer, have a prolonged incubation phase,” says pulmonologist Avi Spira, global head of the LCI. “So there's a significant window of time in which one can intercept the disease before it becomes clinical.”

Johnson & Johnson already plays a leading role in lung cancer prevention through its smoking cessation products, such as chewing gums and patches. Its scientists are developing new behavioural science-based approaches for those seeking to quit. The company also established a collaboration with a California-based digital health startup on a system that combines a carbon monoxide breath sensor with a smartphone coaching app to provide feedback to help users kick their tobacco habit.

Not all lung cancers can, however, be prevented. The next best thing is to identify and treat precursors of the disease as early as possible. “Cancers become more complex and harder to treat as they progress, so the earlier we can get to them, the better,” says Lebowitz.

As part of such efforts, Spira is working with a team at Boston University on the Pre-Cancer Genome Atlas (PCGA) study, which is investigating molecular and cellular changes in people with lung lesions considered to be precancerous. Last year the collaboration published initial results showing that the presence or absence of immune cells in samples taken from pre-cancerous lung lesions of smokers may play a key role in determining whether they progress to become invasive cancers. The researchers concluded that the information may have potential as a biomarker to identify those lesions at risk to progression to invasive cancer and may guide development of pharmaceutical approaches for intercepting those lesions.

The LCI is also involved in research involving around 1,000 current and former military personnel seeking to identify blood and airway-based molecular biomarkers that can distinguish benign vs. malignant lung nodules on CT scans. The hope is that the study will identify non-invasive biomarkers to help refine screening criteria and detect lung cancers earlier.

Complementing such screening efforts, is the use of artificial intelligence to analyse the data. Some research suggests machine-learning systems can outperform human radiologists and pathologists in the diagnosis of some lung cancers by looking for shape, density and texture patterns associated with the disease in datasets from previous patients.

Another arm of the company’s approach is the use of robotic platforms for diagnosis and intervention. Last year, Johnson & Johnson acquired California-based Auris Health and its Monarch^® robotic-assisted bronchoscope system which provides visualization of and access to patient airways for diagnostic and therapeutic procedures. The US Food and Drug Administration (FDA)-cleared device has already been used in more than 4,000 procedures and is the subject of ongoing clinical development activities. In July, FDA granted Johnson & Johnson’s subsidiary Ethicon Breakthrough Designation for Monarch-enabled NeuWave™ Microwave ablation technology, which is currently under development. The hope is to bring these devices together for potential lung intervention solutions in the future

Breast and colorectal cancer screening have helped doctors detect and treat those diseases earlier, leading to significant improvements in survival rates. The combination of improved scientific understanding of precursors and biomarkers, along with technological advances in imaging, mean that reaching and targeting pre-cancerous abnormalities is now possible. Spira hopes that similar advances could bring benefits in lung cancer too.

“We now have a better understanding of the biology of pre-cancer and early cancer including genomic changes and the role of the immune microenvironment, giving us some targets to go after to intercept the disease,” says Spira.

Genomic approach

Alongside prevention and interception, Janssen is making progress in developing treatments targeting gene variants and genetic driver pathways such as the mutations that cause constitutive activation of the oncoproteins EGFR and KRAS. The Janssen Oncology team is also investigating therapies that rely on synthetic lethality, whereby cancer cells with mutations in one gene can be killed by targeting a separate, related gene. Patients have benefitted significantly from targeted therapies, however these often become less effective as resistance develops. Janssen is working to overcome this problem through bispecific therapies that target more than one pathway.

The company is also investigating lung cancer immunotherapies, such as re-directing the immune system to target lung cancer cells with tumour-associated antigens. Some innovative directions may require delivering immunotherapies directly to the site of the tumour or pre-malignant abnormality to activate an immune response. “That’s not easy,” says Lebowitz. “However, as a company, we are well positioned to bring these approaches, the drugs and the devices together, to achieve this goal to get the immune system to recognize and attack malignant cells.”

Spira adds, “Johnson & Johnson is unique in having consumer products, medical devices and pharmaceuticals all under one umbrella. If you can combine and integrate those three sectors, you can deliver more holistic solutions along the patient journey.”

Lung cancer is not the first area where Johnson & Johnson has pursued interception. With ongoing clinical studies in colorectal cancer and multiple myeloma interception, Johnson & Johnson hopes that the lessons learned from these programs can be applied to lung cancer and perhaps other cancers in the future. And while the tendency to diagnose lung cancer late makes an interception approach potentially attractive, the company’s greater emphasis on interception is not without challenges. Trials can take longer and endpoints are sometimes less clear-cut. This can make demonstrating the strategy’s value more difficult, yet a worthy endeavour when considering the potential to transform the trajectory of disease.

Lebowitz acknowledges that taking a different path comes with risks. He believes, however, that advances in understanding cancer biology and in the technologies needed to tackle them makes calculated risks worthwhile, given potential for a step change in patient outcomes.

“There are inherent risks when you’re doing something that hasn’t been done before,” says Lebowitz. “Cancer interception may not be the easiest thing to do, but if you really want to have an impact on people’s health, you have to take new approaches.”