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 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