A Blood Tumour Mutational Burden Test Predicts Immunotherapy Response in Stage 4 Lung Cancer

Patients with stage 4 non-small cell lung cancer (NSCLC) and liquid biopsy (a blood test) measurements of tumour mutational burden (Tumor Mutational Burden, TMB) that were high were found to benefit significantly more from immunotherapy and to live longer with this treatment. This study was published by Aggarwal and colleagues in Clinical Cancer Research on 26 February 2020.

- Related topic: What Is Tumour Mutational Burden? Its Importance

Some patients benefit from immunotherapies, while others do not. There is an important need to identify new, non-invasive biomarkers to help us select the treatment with the best chance of success for each patient, and liquid biopsies are now a tool to help us do this.

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Study Results

• Patients who obtained a durable benefit from treatment had a higher median tumour mutational burden than those who did not achieve a durable clinical benefit: compared with 21.3 mutations/Mb, 12.4 mutations/Mb.
• Where the number detected per megabase (Mb) of mutations was above 16, the 24 patients had a median progression-free survival of 14.1 months; in contrast, the other group of 24 patients with the lowest tumour mutational burden had a median of 4.7 months.
• For the group with high tumour mutational burden, median overall survival was not reached because more than half of the patients continued to respond to treatment; median overall survival in the low tumour mutational burden group was 8.8 months.

A Simple Blood Test Can Screen for Mutations in 500 Different Genes

The researchers used this "liquid biopsy" panel to measure tumour mutational burden in 66 patients, 52 of whom were evaluable for this study. Median tumour mutational burden was 16.8 mutations per megabase (Mb) and was significantly higher in patients with a durable clinical benefit than in those who did not benefit.

Conclusion

Measuring tumour mutational burden through liquid biopsy and planning immunotherapy accordingly has not yet received FDA approval. However, this study demonstrated the strongest association reported to date between liquid tumour mutational burden and clinical outcomes with immunotherapy in stage 4 non-small cell lung cancer. In the near future, liquid tumour mutational burden may begin to be used to select treatment in oncology practice.