Results: Patient with lung cancer (non-small cell) and a somatic (tumour) ALK rearrangement

A 42-year-old male who has never smoked is diagnosed with metastatic lung cancer (non-small cell). Somatic (tumour) testing via a multi-target massively parallel sequencing (sometimes called next-generation sequencing) panel reveals an EML4-ALK fusion gene.

The ALK gene

• Rearrangements of ALK are found in around 5% of lung adenocarcinomas.
• The most common fusion partner is EML4.
• Rearrangements can be detected by fluorescent in situ hybridisation (FISH), immunohistochemistry (if appropriately validated) or massively parallel sequencing.
• ALK rearrangements sensitise tumours to ALK tyrosine kinase inhibitors (TKIs).

Clinical characteristics of ALK-rearranged lung cancer

• On average, patients with ALK-rearranged lung cancer are younger than those with wild-type ALK and are more likely to be never, light or ex-smokers.
• There is no strong association with gender or ethnicity.
• The vast majority of cases are adenocarcinoma, often containing signet ring cells.
• ALK-rearranged tumours have a higher propensity for central nervous system metastases than wild-type tumours.

Management of the current cancer

• The presence of an ALK fusion gene makes patients eligible for ALK TKI therapy, potentially for both first- and second-line treatment.
• Different ‘generations’ of ALK TKI exist with different receptor specificities, binding affinities (to the ALK protein), central nervous system penetration and clinical efficacy.
• Several agents are licensed and routinely funded in the UK (such as alectinib, brigatinib and ceritinib) for both first- and second-line treatment.

Following progression on first- or second-line therapy

• Resistance to ALK TKIs may result from secondary ALK variants.
• Research is ongoing to explore the sensitivity of different ALK resistance variants to different TKIs.
• Clinical trials may be available for patients who have progressed on ALK TKIs. Some stratify according to molecular testing for secondary ALK variants.

For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.

For clinicians

• NHS England: National Genomic Test Directory
• NICE: All products on lung cancer
• NICE: Guidance relevant to lung cancer
• The European Society for Medical Oncology (ESMO): Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow up (PDF, 71 pages)
• The International Association for the Study of Lung Cancer (IASLC): The IASLC atlas of ALK and ROS1 testing in lung cancer

For patients

• Cancer Research UK: Targeted and immunotherapy treatment for lung cancer