For patients with colorectal cancer
Anti-EGFR antibody based therapies such as cetuximab & panitumumab are commonly used to treat metastatic colorectal cancer. However, if a patient’s tumour contains certain mutations, these therapies simply won’t work. Thus it is important to try to identify these mutations as early as possible in order to start alternative treatment options without delay.
Many clinicians only use a combination of two single gene tests to analyse the KRAS and NRAS (collectively referred to as RAS) genes for activating mutations, as these alone account for the majority of colorectal patients who will not benefit from anti-EGFR therapy. Both these genes are included in all our multi-gene tests, but so are a number of others, such as BRAF, PIK3CA and PTEN – all of which can be important when treating colorectal cancers. This information can help you avoid putting your patient through a treatment that won’t work. Also, if there are no licensed or approved therapies to suit your patient, the tests can help you direct them into the right clinical trial.
For patients with lung cancer
A range of targeted therapeutic agents known as EGFR Tyrosine Kinase inhibitors (TKIs) can be used to treat non-small cell lung cancer. However, these are only effective in patients whose tumours contain certain EGFR gene mutations. Consequently, clinicians often request a single gene EGFR test that can identify the most common of these so called ‘TKI sensitizing’ mutations. Unfortunately though, only a minority of patients will possess these mutations, leaving little or no choice of alternative options for the remaining majority.
All of our multi-gene tests include EGFR and are not limited to detection of only the most common mutations. Furthermore, they include the analysis of a range of other genes that can also drive tumour growth and/or drug resistance in lung cancers in addition to EGFR. These include BRAF, PIK3CA, MET, MAP2K1, STK11, HER2 and PTEN, amongst others. The information gained from analysing these may suggest alternative ‘off label treatment’ and clinical trial options in EGFR negative patients.
Even if your patient has previously had an EGFR single gene test that identified an EGFR TKI sensitizing mutation, our tests can still be useful. This is because in time such patients will unfortunately go on to develop resistance to the first line TKI therapy. In some cases, this will be due to additional mutations in EGFR, such as a change from Threonine to Methionine at codon 790 (often just referred to as T790M), which can be detected by most EGFR single tests and treated with osimertinib, a recently approved 3rd generation EGFR TKI. However, in the same way that not all lung cancer are driven by EGFR mutation, not all EGFR TKI resistance is driven by T790M and tests that only analyse this can give no other information that may help guide options in T790M negative EGFR TKI resistant patients.
For patients with melanoma
BRAF inhibitors are the drugs of choice in treating metastatic melanoma. However, their routine use is only indicated in patients whose tumours contain mutations at one specific site (codon 600) of the BRAF gene. Consequently, clinicians often request a single gene BRAF test that can identify the mutations at codon 600 only. Unfortunately though, less than half of patients will possess this mutation, leaving little or no choice of alternative options for the remainder.
In addition to BRAF codon 600, all our multi-gene tests also assess other BRAF activating mutation sites as well as other genes like NRAS and MAP2K1, which can help direct potential off-label treatment or clinical trial options. Our 50 gene panel can expand these options further by including KIT, GNA11 and GNAQ.
For patients with breast cancer
Our tests can be useful for patients who have been through endocrine or other therapies. For example, they can identify alterations in PIK3CA or AKT1, which would help lead the patient onto clinical trials.
2. Getting more information and options from extended testing (MGP-3)
Our third NGS Multi-Gene Panel (MGP-3) assay extends testing beyond DNA sequencing to include RNA, which constitutes the currently recommended molecular method for assessing gene fusions. Unfortunately, to date there are only a few approved targeted therapies in the UK for tumours driven by gene fusion events (predominantly ALK and ROS1 in non-small cell lung cancer) and as such most routine testing is performed using more traditional techniques such as IHC & FISH. However, many ongoing clinical trials are looking at the efficacy of new agents targeting other gene fusions, notably RET and NTRK in a wider range of cancer types. In certain cancers MGP-3 may be the initial ‘go to’ assay of choice, but for others where very commonly assessed variants such as those in KRAS account for a high proportion of cases, reflex testing with MGP-3 in otherwise pan-negative cases may be the most appropriate option.
3. Getting answers fast from our rapid turn round single gene tests
Metastatic Colorectal (mCRC) Screen: Mutations in KRAS are the cause of many colorectal cancers. We can test KRAS quickly to identify whether your patient has an activating KRAS mutation and consequently will not benefit from anti-EGFR therapy. If KRAS mutation is NOT the cause of your patient’s cancer, it’s obligatory (in order to meet UK best practice guidelines) that we reflex at least to analysis of NRAS, though we also include BRAF – as collectively these account the majority of patients who would likely not respond or potentially only respond poorly to anti-EGFR therapy. Please note that KRAS positive patients will not routinely be tested for NRAS/BRAF as well.
Melanoma Screen: BRAF inhibitors are the drugs of choice in treating metastatic melanoma. However, their routine use is only indicated in patients whose tumours contain mutations at one specific site (codon 600) of the BRAF gene. To enable suitable patients to access this treatment fast we offer codon 600 only analysis in rapid turn-round format.
Non-Small Cell Lung Cancer (NSCLC) Screen: EGFR TKIs are the drugs of choice in treating NSCLC. However, their routine use is only indicated in patients whose tumours contain mutations at specific sites within the EGFR gene. To enable suitable patients to access this treatment fast we offer analysis of the most commonly mutated loci in rapid turn-round format.
With all our rapid turn-round single gene test options, we will deliver the results within 2 working days, subject to the supplied sample meeting the necessary acceptance criteria.
Given that these rapid turn-round single gene tests are as not comprehensive as multi-gene options, they should only be used when circumstances mean that time is critical. Furthermore, in certain cancer types you may still wish to consider reflexing to multi-gene testing in the event that single gene analyses prove negative.