Companion diagnostic testing for specific genes

Mutations that occur in tumours as part of disease progression that activate specific signalling pathways may be actionable targets for therapeutic agents that disrupt these pathways.

Companion diagnostics are tests developed in association with specific therapies to determine which patients are most likely to benefit from treatment with these agents. This assists the clinician in personalising patient treatment plans and are often required for assessing the eligibility of a patient to access these targeted therapies under the Pharmaceutical Benefits Scheme (PBS).

Mutational Profiles of tumour DNA, which look at many genes in various pathways, may also assist in direct patient management, determining prognosis and prioritising anti-tumour therapies.

RAS (KRAS, NRAS)

Testing for mutations in KRAS and NRAS in metastatic colorectal tumour tissue may assist in assessing which patients will likely benefit from anti-EGFR therapeutics, such as Cetuximab or Panitumumab, that are targeted to the RAS pathway. Lack of activating mutations defines eligibility for accessing these therapies under the Pharmaceutical Benefits Scheme (PBS) when requested by an appropriate specialist. An MBS rebate is available for this purpose. Treatments with these targeted therapies either as a single agent, or in combination with chemotherapy, reduce the risk of disease progression but are only beneficial in those patients with tumours without a KRAS or NRAS mutation. Targeted testing of exons 2, 3 and 4 in detects mutations in each of the KRAS and NRAS gene at codons 12, 13, 61, 117 and 146.

BRAF

Testing for the BRAF V600 somatic mutations (V600E and V600K) in metastatic melanoma tumour tissue may assist in determining which patients will likely benefit from anti-BRAF therapeutics and, if a V600 mutation is present, whether they will be eligible for accessing the anti-BRAF agent Dabrafenib under the PBS when requested by an appropriate specialist. An MBS rebate is available for this purpose. Patients with BRAF V600 mutations are suitable for treatment with anti-BRAF therapeutics. BRAF mutations are found in 60-70% of melanomas, 45% of papillary thyroid cancers and 15% of colorectal cancers. BRAF V600E mutations are associated with resistance to the tyrosine kinase inhibitors Cetuximab or Panitumumab.

EGFR

EGFR-mutant NSCLC is defined as a distinct, clinically relevant subset of lung cancer. These tumours are histologically similar to adenocarcinomas, however they differ in their sensitivity to treatment with EGFR tyrosine kinase inhibitor therapies such as with Erlotinib or Gefitinib. Some mutations in the EGFR gene confer sensitivity to TKIs, whereas others may confer resistance. Therefore, the mutation status of EGFR can be a useful marker by which patients are selected for EGFR-targeted therapy. Testing for EGFR mutations in exons 18, 19, 20 and 21 in non-small cell lung cancer tumour tissue may assist in determining which patients will likely benefit from these treatments, and determine their eligibility to saccess treatment under the PBS when requested by an appropriate specialist. An MBS rebate is available for this purpose.