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About ALK+ LC
ALK-positive lung cancer is a rare type of non-small cell lung cancer (NSCLC) in which there is an abnormal fusion of the anaplastic lymphoma kinase (ALK) gene.
What is ALK-positive Lung Cancer?
ALK-positive lung cancer is a rare type of non-small cell lung cancer (NSCLC) in which there is an abnormal fusion of the anaplastic lymphoma kinase (ALK) gene and another gene, often (about 90%) echinoderm microtubule-associated protein-like 4 (EML4).
This fusion causes cell enzymes (specialized proteins) to send signals to cells instructing them to divide and multiply more quickly than usual. The result: the spread of cancer.
ALK-positive lung cancer is an acquired condition but it is not known exactly what triggers this. It is believed that the condition is not inherited and cannot be handed down to children.
The ALK mutation can occur anywhere in the body, including blood, but is most common in the lung.
There are about 49,000 new cases of lung cancer in the UK each year. About 9 out of 10 will be non-small cell lung cancer (NSCLC).
It is estimated that in the UK about 2% of NSCLC cases will have the ALK mutation.
About 40% will be diagnosed at an early stage and about 60% at an advanced stage.
Source: Thai, Solomon et al. The Lancet 2021
Certain people are more likely to have cancer cells with the ALK fusion gene:
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Younger Patients (55 years and under)
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People who have never smoked (or smoked very little)
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People of East Asian ethnicity
An X-ray, CT scan or PET scan may identify lung cancer but an ALK rearrangement has to be diagnosed through genetic testing (also known as molecular profiling). Healthcare providers obtain a sample of a lung tumour for a tissue biopsy or may examine a blood sample obtained for a liquid biopsy. These samples are checked for biomarkers that show the ALK rearrangement is present.
Smoking History
Age at Diagnosis
Data from our members
Patients diagnosed at Stages 1, 2 and 3a are likely to be offered surgery, radiotherapy or chemotherapy with curative intent. They may also be prescribed a TKI (see below).
Patients diagnosed at Stages 3b and 4 are likely to be treated with oral drugs that work to shrink the tumours and inhibit their growth. These drugs are called Tyrosine Kinase Inhibitors (TKIs).
Five TKIs have been approved by the National Institute for Health and Care Excellence (NICE) in England and Wales for treating advanced ALK-positive lung cancer. The Scottish Medicines Consortium has made similar approvals in Scotland.
The terms of NICE approval depend on the pharmaceutical company’s submission and this can affect the order (pathway) in which drugs can be used.
Patients who are diagnosed at Stage 4 will usually start their treatment with Alectinib, Brigatinib or Lorlatinib.
A 4th generation TKI and other possible treatments are currently under trial.
It’s important to keep in mind that TKIs are not a cure for lung cancer, but rather a treatment that allows a tumour to be kept in check.
1st Generation
Crizotinib
2nd Generation
Alectinib - Brigatinib - Ceritinib
3rd Generation
Lorlatinib
Tumours can often be managed for years with these drugs, reducing the likelihood that the cancer cells will spread. Hopefully, one day, lung cancer may be treated like other chronic diseases.
TKIs can have immediate beneficial effects for some patients by significantly reducing the size and number of lesions but it is essential that patients are regularly monitored. Leading experts recommend that CT scans should be carried out every three months.
Lung cancer, and in particular ALK-positive lung cancer, often progresses to the brain. About 26% of patients will have brain metastases at diagnosis and about another 20% will develop brain metastases with 2 years. We consider that it is best practice for patients to receive a brain MRI at diagnosis and, if no brain lesions are found, at six-monthly intervals thereafter. If brain lesions are found, MRI scans should be carried out every three months. Unfortunately, there are no national guidelines.
ALK-positive patients have an elevated risk of developing a venous thromboembolism (blood clot) and about 18% are likely to do so within 12 months of diagnosis and about 30% within 5 years.
Patients taking tyrosine kinase inhibitors (TKIs) should have regular electrocardiograms (ECGs) to monitor for potential cardiac side effects.1 An ECG should be taken before treatment starts to establish a base line and repeated within the next 4 weeks to detect any early changes. Thereafter, ECG may be performed at 3 – 6 month intervals, depending on the patient’s risk factors and the TKI’s cardiac risk profile. High risk patients may have monthly ECGs.
Lung cancers may initially respond very well to targeted therapy medications. However, patients almost always become resistant to the medication over time and their cancer progresses.
If patients develop resistance to an ALK inhibitor, their healthcare provider may try a new medication or, If the progression is localised, radiotherapy may be offered. Chemotherapy may also be offered.
Like other cancer medications, it can be expected that TKIs will produce side effects, although these are likely to be much less than the side effects of chemotherapy. Each of the TKIs will produce its own side effects – some effects may be mild, others may be uncomfortable and disrupt everyday life and others may be severe.
Blood tests should be taken at regular intervals to ascertain whether the treatment is affecting vital organs. It may be necessary to reduce dosage, to pause treatment or, in severe cases, to change treatment.
Results from a trial of the 3rd generation TKI, Lorlatinib, indicated that 6 out of 10 patients did not have any progession of their cancer after 5 years, when the drug was used as the first line of treatment. At present, it is not possible to predict how long individual patients will survive.
TKIs bring the possibility of having a good quality of life and of living progression-free for many years.
Molecular Mechanisms and Treatment Strategies of ALK-Positive Lung Cancer: A Beginner's Guide for Patients, Their Families and Carers
This paper has been produced by Elena Klenova, Emeritus Professor, School of Life Sciences, University of Essex, and an ALK-positive patient.
Although it is a beginner's guide, it is quite technical in parts. However, section 11 (Current and Future Treatment Perspectives) and section 12 (Discussion on Socio-Economic, Health and Research Challenges) are well-worth reading.
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