Lung cancer refers to tumors originating in the lung parenchyma or within the bronchi.¹ Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, making up approximately 85% of lung cancers, and is defined as any type of epithelial lung cancer other than small cell lung cancer (SCLC).^2,3 

NSCLC can be further subdivided on the basis of histological features into several categories, the most common of which are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.⁴ Large cell carcinoma has been defined in the past as a tumor that lacks morphologic evidence of either glandular or squamous differentiation.⁵

However, increasing evidence shows that a large proportion of these tumors can be subtyped further using modern immunohistochemical and molecular methods.⁵ 

Lung cancer may present with symptoms, such as cough or chest pain, or be found on chest imaging, with additional investigations aiming to confirm the diagnosis and determine the extent of the  disease.⁶ Factors such as stage, histology, presence and type of mutation, and the presence of comorbidities will define the prognosis and treatment options available to a patient.^7–10

Determination of stage has important prognostic and treatment implications.⁷ Procedures used to establish stage include a physical examination and radiological assessment.^{​​​​​​​11,12} The disease is staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM system, which is based on:¹³

• Size and extent of main tumour (T)
• Spread to nearby lymph nodes (N)
• Metastasis (M) to distant sites

Accurate lung cancer staging is vitally important because treatment options and prognosis differ significantly by stage.⁷ Most patients present with advanced stages of lung cancer,¹ limiting their treatment options and negatively impacting their prognosis¹⁴

Over the last two decades, our understanding of the pathogenesis of non-small-cell lung cancer (NSCLC) has developed significantly, greatly changing the therapeutic landscape of this field.^15,16

The discovery of oncogenic drivers has played a pivotal role in the management of advanced NSCLC.¹⁷ The introduction of targeted agents, accompanied by the discovery of activating mutations, has furthered our understanding of oncogene-driven carcinogenesis.¹⁷ Stratifying patients, first by mutational status and then by other factors, ensures that an expanding range of treatment options are now available to patients and the treatment will depend on a range of unique factors, such as:^17–21

• Stage of cancer
• Oncogenic driver mutation
• Patient comorbidities

The diversity of non-small-cell lung cancer (NSCLC) has led to further subclassification of this disease beyond histological subtypes.²² Molecular analysis of genetic alterations in NSCLC, especially common in those with adenocarcinoma, has shown that lung cancer can also be divided by molecular subtypes.²² This has revolutionized targeted treatment options for patients and improved outcomes.^23,24 The shift from histological to molecular subtypes is summarized in Figure 1, highlighting the diversity of molecular subtypes that exist within the patient population.²⁵

Adapted from Chan BA and Huges BGM. Transl Lung Cancer Res 2015;4(1):36–54. ²⁵

Survival for patients following a non-small-cell lung cancer (NSCLC) diagnosis varies, depending on how advanced their cancer is, the histological and molecular subtype, gene changes in the cancer cells, and what treatment they are receiving.^26–29 More advanced disease will significantly decrease survival rates and the histological diagnosis also impacts the survival probability of the patient.^26,27

In mutation-driven NSCLC, the survival rate varies by treatment option, highlighting the value of targeted therapy for the patient’s specific mutation over chemotherapy.²⁸

Anaplastic lymphoma kinase (ALK) gene rearrangement is a driving mutation underlying the development of non-small-cell lung cancer (NSCLC) and has been identified in 3−5% of NSCLC cases.^30,31 ALK rearrangement appears to be more common in younger patients and never or light smokers diagnosed with adenocarcinoma.³⁰


The first targeted treatment for advanced ALK+ NSCLC, crizotinib, was approved by the US Food and Drug Administration (FDA) in 2011, only 4 years after the discovery of ALK rearrangement as a potential oncogenic driver in NSCLC.3^32,33

Please refer to the full prescribing information for further information regarding each therapy.

First described in 2007, c-ros oncogene 1 (ROS1) rearrangements are present in 1-2% of non-small-cell lung cancer (NSCLC), with an estimated 10,000–15,000 new cases worldwide every year.³⁴ Patients are often never or light smokers, with the cancer frequently diagnosed at a young age.³⁴ Many different ROS1 fusion partner genes have now been reported in lung cancer, but the exact mechanism of ROS1 kinase activation in the fusion proteins has not been established.³⁵

Please refer to the full prescribing information for further information regarding each therapy.​​​​​​​

Click here to view Pfizer NSCLC Portfolio