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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 lung 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.
Non-small cell lung cancer pie chart
International studies indicate that about 5% of non-small cell lung cancer is due to the ALK rearrangement This would equate to several thousand new cases each year in the UK. However, our analysis of prescribing data suggests that the number is much lower. A UK cancer centre has reported that its ALK-positive patients comprise 2% of their NSCLC cases.
The ALK fusion has many variants which may be why patients respond differently to treatments.
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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Women
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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 3 are likely to be offered surgery, radiotherapy or chemotherapy with curative intent. They may also be prescribed a TKI (see below).
About 85% of ALK-positive patients are diagnosed at Stage 4 and are likely to be treated with oral drugs that work to shrink the tumours. These drugs are called Tyrosine Kinase Inhibitors (TKIs).
Five TKIs have been approved by the National Institute for Health 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 depends on the pharmaceutical company’s submission and this can affect the order (pathway) in which these drugs can be used. A table showing these pathways is at the foot of our NICE page.
Currently, most patients in England and Wales who are diagnosed at Stage 4 will start their treatment with Alectinib or Brigatinib.
A 4th generation TKI and other possible treatments are currently under trial.
1st Generation
Crizotinib
2nd Generation
Alectinib - Brigatinib - Ceritinib
3rd Generation
Lorlatinib
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. 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 35% of patients will have brain metastases at diagnosis. 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. 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 stop the treatment.
Recent research in the UK suggests that the median survival for people with stage 4 ALK-positive lung cancer is 6.2 years, i.e over half of patients will survive longer than this.
Of course, whatever the median survival rate is, half will live longer, some much longer, and half will live shorter, some much shorter. 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 without serious side effects for many years.
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