Are liquid biopsies a surrogate for tissue EGFR testing?

Molecular profiling has changed the treatment landscape in advanced non-small-cell lung cancer. Accurately identifying the tumours that harbour sensitizing EGFR mutations, the most common targetable molecular alteration, as well as those with acquired resistance mutations (e.g. T790M) on treatment is a high clinical priority. The current clinical gold standard is genotyping of tumour specimens. However, the practical utility of this approach is limited by the lack of available tissue and the potential complications associated with biopsies. With the advent of newer sequencing assays, it has become feasible to assess tumour genomics via a blood sample, termed a ‘liquid biopsy’. Researchers from UCLA School of Medicine summarize the available techniques for liquid biopsies and their applicability for detecting sensitizing and resistance EGFR mutations and how these results may be used for making treatment decisions.

Liquid biopsy for discovery of actionable EGFR mutations, monitoring response to therapy,
and detecting development of TKI resistance

Liquid biopsy carried out at diagnosis guides treatment with a TKI to target actionable mutations (A). ctDNA levels can correlate to response to TKIs (B). At progression, as ctDNA levels rise, one would ideally obtain a repeat tissue biopsy to guide next treatment decision (C). However, even when a tissue biopsy is carried out, due to tumour heterogeneity, it may miss mutations due to sampling bias (D).