First-line treatment options for advanced Non- Small Cell Lung Cancer (NSCLC) harbouring anaplastic lymphoma kinase (ALK) gene rearrangement

Around 5% of NSCLC tumours harbour a novel fusion oncogene echinoderm microtubule-associated protein-like 4 gene (EML4) fused with ALK gene. These tumours are highly sensitive to therapy with ALK inhibitors.

Crizotinib is a multikinase inhibitor of ALK tyrosine kinase, mesenchymal epithelial transition growth factor (c-MET) and ROS1 receptor tyrosine kinase. When compared to second line chemotherapy (pemetrexed or docetaxel) in a phase III randomised controlled trial, treatment with crizotinib was associated with a significantly higher response rate of 65% vs. 20% (p < 0.001), progression free survival of 7.7 months vs. 3 months (HR 0.49 95% CI 0.37 0.64 p 0.001) and improvement in global quality of life.23

Ceritinib is a second generation ALK inhibitor with clinical activity demonstrated in patients whom have received prior crizotinib and in those who had not received crizotinib.8

Cost Effectiveness

The cost effectiveness of EML4-ALK fusion testing and first line therapy with crizotinib was analyzed from the perspective of the Canadian public healthcare system. Molecular testing and first line therapy with crizotinib cost an additional USD $208,708 per QALY gained compared with standard of care with no testing and no crizotinib treatment.24The authors concluded that EML4-ALK fusion molecular testing and targeted therapy with crizotinib in their setting of low prevalence of EML4-ALK fusion gene and the high cost of crizotinib is not cost effective.24

Recommendations on First Line Treatment Options for Advanced NSCLC Harbouring ALK Gene Rearrangement

1. The workgroup unanimously recommends consideration of enrolment into clinical trials or to adopt NCCN guidelines for the consideration of crizotinib as first line treatment for ALK gene rearranged advanced lung cancer (category I). The workgroup recommends a discussion with patients on the cost implications of the option of crizotinib.

2. Patients who are intolerant to crizotinib may be switched to Ceritinib (category 2A).