There is little doubt of the scale of the unmet needs in lung cancer. According to the World Health Organization, it is the world’s most deadly cancer, accounting for almost three times as many deaths as breast cancer, the next most common . In 2018, lung cancer accounted for approximately 2.1 million cases and 1.8 million deaths, worldwide .
Why is this the case? There are of course a number of different factors at play. Many patients have advanced lung cancer (stages IIIb/IV) at the time of diagnosis, a situation not helped by the fact that screening rates for lung cancer in high-risk patients are significantly lower than other cancers, such as breast or prostate [2,3]. Additionally, funding for lung cancer research is comparatively low – with the lowest spend relative to disease burden compared with breast or prostate cancers, and roughly the same as colorectal, which kills less than third as many individuals .
This results in a lung cancer landscape that demands for us all to take bold action – not just through our ongoing efforts to develop innovative treatments, but by finding additional solutions that target the root cause of problems that lead to this lethal disease and enable earlier and more effective diagnosis.
If we want to help bring about real change in lung cancer, then we need a holistic yet precise approach, with a vision as simple as it is ambitious: to effectively prevent or intercept the disease, depending on its stage. This could be achieved through a wide range of strategies, including testing and screening; identifying people with early-stage lung cancer to enable curative intervention; challenging and changing policy; partnering with relevant organizations and institutions; and investing in research to improve patients’ treatment options.
But of course, on the most fundamental level, the better we understand the disease, the better we will be able to target it through those strategies.
Understanding the molecular biology of lung cancer
In recent years, understanding of the molecular biology of non-small cell lung cancer (NSCLC), which constitutes most cases of the disease (85%), has developed from a ‘one size fits all’ mentality towards a more refined method of disease classification, underpinned by identification of specific genetic alterations, and with the development of targeted therapies guided by molecular stratification . While lung cancer has seen substantial improvements in outcomes through the evolution of precision medicine, prognosis remains poor for some patients with advanced NSCLC .
For example, EGFR-mutated NSCLC is characterized by a wide range of mutations across exons 18–22 of the EGFR gene . These mutations possess distinct characteristics that have implications for diagnostic testing and clinical practice, and each in turn has its own implications for patient outcomes . Take EGFR exon 20 insertion-positive NSCLC, which is a particularly aggressive form of lung cancer, with an estimated median survival rate of just 16 months – around half of the survival rate reported for patients harboring more common EGFR tyrosine kinase inhibitor (TKI)-sensitive mutations (32–39 months) [6–8].
While existing targeted EGFR TKI therapies can provide an effective treatment option for patients with the more common types of activating EGFR mutations, these may not work for people with exon 20 insertions [9,10]. The result is that patients with lung cancer who have EGFR exon 20 insertion mutations currently have no targeted therapy options that are specifically approved for this indication [5,11].
The lack of treatment options for these patients is a very difficult thing to confront, and I have heard from healthcare professionals and patients alike just how much of an impact the news of their diagnosis can have. It is essential that this area of unmet need is addressed – which is why it forms an important part of our comprehensive lung cancer clinical development program at Janssen (Beerse, Belgium).
Advancements in diagnostic testing for lung cancer
Beyond the need to find effective, targeted therapies for patients with the greatest unmet need, improved early diagnostic testing is also critical; without accurate and efficient biomarker testing, patients who are eligible for certain targeted therapies may go undetected [12,13].
We know that when a gene alteration is identified in patients with NSCLC that has a specific targeted therapy that is administered, this is associated with increased progression-free survival and a substantial reduction in the risk of death, compared with those with no detectable alteration . Selection of targeted treatment is dictated by the presence of molecular disease drivers, which are identified via genetic testing, and evidence-based guidelines stipulate that genetic testing should be performed on patients’ tumors when they are diagnosed with advanced disease .
However, results from a survey of International Association for the Study of Lung Cancer members and healthcare professionals (2537 questionnaires across 102 countries; 2012–2013) showed that a third (33%) of respondents were unaware of the most recent guidelines for testing, over one third (37%) reported that they found interpretation of test results challenging and nearly two thirds (61%) believed that less than half of patients in their country are sent for molecular testing .
At Janssen, and more broadly at Johnson & Johnson (NJ, USA), we’re committed to developing solutions to prevent and intercept this disease. Over the last two years, the Lung Cancer Initiative, set up by Janssen’s parent company Johnson & Johnson, has supported several advancements towards this end, including :
- a collaboration with a genomic diagnostics company, Veracyte (CA, USA), to co-develop the first non-invasive nasal swab diagnostic and a next generation bronchial diagnostic test for the early detection of lung cancer . Additionally, Johnson & Johnson acquired Auris Health’s MONARCH™ Platform robotic technology, which provides access to lung cancer lesions for precise diagnostic and therapeutic procedures . Both of these innovative technologies could give us a better chance of intercepting cancers at an earlier stage, enabling potentially curative treatments to be initiated
- development of the Pre-Cancer Genome Atlas, in collaboration with Boston University (MA, USA), the largest repository of lung squamous cell carcinoma and premalignant lesions in the world. This will help to define determinants of disease progression and enable development of targeted interception strategies . Recently, published data from this collaboration showed that the presence or absence of immune cells in pre-cancerous lung lesions may provide critical information as to whether the lesion will progress toward invasive lung cancer 
- facilitating the Detection of Early Cancer Among Military Personnel (DECAMP) studies, with the goal of enabling the development, integration and validation of molecular and imaging-based biomarkers to improve lung cancer detection 
Diagnosing and treating early to give patients the gift of time
If we are to improve outcomes in lung cancer, we need to be intervening throughout the disease pathway, working together to effectively identify and treat patients from the very early stages of the disease. This way, we’ll be able to help achieve as much quality time as possible for every patient. There are already so many promising developments on the horizon, but at the same time so much still left to do. It will take everything – from initiatives like the Lung Cancer Initiative, to new targeted therapies, to cutting-edge diagnostic tools – to transform the lung cancer disease landscape.
For more information about Janssen Oncology visit: https://www.janssen.com/uk/our-focus/oncology
The opinions expressed in this Editorial are those of the author and do not necessarily reflect the views of Oncology Central or Future Science Group.
CP-170585 / September 2020
- World Health Organization. Cancer. Available at: www.who.int/news-room/fact-sheets/detail/cancer [Accessed August 2020].
- Knight SB, Crosbie PA, Balata H, Chudziak J, Hussell T and Dive C. Progress and prospects of early detection in lung cancer. Open Biol. 7(9), 170070 (2017).
- Detterbeck FC, Mazzone PJ, Naidich DP, Bach PB. Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. 143(5) E78S–E92S (2013).
- Carter AJR and Nguyen CN. A comparison of cancer burden and research spending reveals discrepancies in the distribution of research funding. BMC Public Health. 12, 526 (2012).
- Vyse S and Huang PH. Targeting EGFR exon 20 insertion mutations in non-small-cell lung cancer. Signal Transduct. Target Ther. 4(5) (2019).
- Oxnard GR, Lo PC, Nishino M et al. Natural history and molecular characteristics of lung cancers harbouring EGFR exon 20 insertions. JTO 8(2), 179–184 (2013).
- DerSarkissian M, Li S, Galaznik A et al. HSR19-084: real-world treatment patterns and clinical outcomes in non-small-cell lung cancer patients with EGFR exon 20 insertion mutations. JNCCN 17(3.5) (2019).
- Ramalingam SS, Vansteenkiste J, Planchard D et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. Engl. J. Med. 382, 41–50 (2020).
- Crossland V, Galaznik A, Lin HM et al. HSR12-082: epidemiological findings and outcomes in non-small-cell lung cancer patients with exon 20 insertion mutations: a meta-analysis. JNCCN 17(3.5) (2019).
- Hirano T, Yasuda H, Tani T et al. In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer. Oncotarget. 6, 38789–38803 (2015).
- Baraibar I, Mezquita L, Gil-Bazo I et al. Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC. Rev. Oncol. Hematol. 148, 102906 (2020).
- Riess JW, Gandara DR, Framptom GM et al. Diverse EGFR exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC. JTO 13(10), 1560–1568 (2018).
- Feng Y, Feng G, Lu X et al. Exploratory analysis of introducing next-generation sequencing-based method to treatment-naïve lung cancer patients. JTD 10(10), 5904–5912 (2018).
- Smeltzer MP, Wynes MW, Lantuejoul S et al. The international association for the study of lung cancer global survey on molecular testing in lung cancer. JTO doi: 1016/j.jtho.2020.05.002 (2020) [In press].
- Johnson & Johnson. Johnson & Johnson Lung Cancer Initiative. Available at: jnj.com/tag/johnson-johnson-lung-cancer-initiative [Accessed August 2020].
- Veracyte. Veracyte announces strategic collaboration with Johnson & Johnson innovation in battle against lung cancer. Available at: www.investor.veracyte.com/news-releases/news-release-details/veracyte-announces-strategic-collaboration-johnson-johnson [Accessed September 2020].
- CISON. Johnson & Johnson Announces Agreement to Acquire Auris Health Inc. Available at: www.prnewswire.com/news-releases/johnson–johnson-announces-agreement-to-acquire-auris-health-inc-300794960.html [Accessed September 2020].
- The BRINK. BU and Johnson & Johnson Innovation Team Up to Fight Lung Cancer. Available at: www.bu.edu/articles/2018/bu-johnson-johnson-innovation-fight-lung-cancer/ [Accessed September 2020].
- Beane JE, Mazzilli SA, Campbell JD et al. Molecular subtyping reveals immune alterations associated with progression of bronchial premalignant lesions. Nat. Comm. 10, 1856 (2019).