The topic of companion diagnostics has been of continuing interest for me. I have posted a number of notes about this type of lab test (see, for example: More Details About Roche's Companion Diagnostics Strategy; A Closer Look at Companion Diagnostics Strategies; Consideration of a Broader Definition for "Companion Diagnostics"; Some Interesting Insights into Companion Diagnostics; Companion Diagnostics Gains Wider Acceptance in FDA Despite Challenges). Now comes news of a new collaboration between AstraZeneca and Roche on a diagnostic test to be used as a companion for AZ9291, an investigational compound (see: AstraZeneca, Roche Collaborate on Companion Diagnostic Test). Below is an excerpt from the article:
AstraZeneca announced it has entered into collaboration with Roche to develop a plasma-based companion diagnostic test to support AZD9291, AstraZeneca’s investigational compound in clinical development for non-small-cell lung cancer (NSCLC). The companion diagnostic test is designed to identify epidermal growth factor receptor (EGFR) mutations in both tumor tissue and plasma derived from patients with NSCLC, and to optimize the clinical development of AZD9291 for patients who are resistant to first-generation EGFR tyrosine kinase inhibitors (TKI). Currently, patients who have been treated with EGFR-TKIs in whom the disease has progressed have to undergo a repeat biopsy to assess whether they have a specific mutation, T790M. Diagnostic tests based on circulating DNA (ctDNA) in plasma samples provide an alternative method of identifying the T790M mutation....“Currently, late-stage lung cancer patients have to undergo surgery to collect tissue from a tumor so it can be sent for molecular testing,” said Paul Brown, head of Roche Molecular Diagnostics (RMD). “In some cases, collecting enough tissue for testing is not possible. This collaboration will enable molecular testing through plasma specimens and provide the information needed to inform treatment decisions without the complications of surgery, consequently increasing the level of care clinicians can give to the patient.” NSCLC represents approximately 80 to 85% of all lung cancers. Unfortunately, at the time of diagnosis approximately 70% of NSCLC patients have developed advanced or metastatic disease not amenable to surgical resection.
To summarize, AstraZeneca is working with Roche on a companion diagnostic to identify epidermal growth factor receptor (EGFR) mutations in both tumor DNA as well as in DNA circulating in plasma. The source of the latter is circulating tumor cells (ctDNA). Analysis of plasma ctDNA to detect tumor recurrence avoids the need to biopsy tumor tissue and thus the complications of additional surgery. This article illustrates the dual use of companion diagnostics. First of all, the test can be used to determine whether a patient is a candidate for a particular drug therapy -- compound AZ9291 in this case. The fact that the drug does not yet have a proprietary name is evidence of the very early stage at which the companion diagnostic is being developed. Secondly, the diagnostic test can also be used to identify circulating tumor DNA in the plasma.
NSCLC, a confusing term, is the most common type of lung cancer. Unfortunately and as noted above, some 70% of NSCLC patients have advanced disease at the time of diagnosis that is not amenable to surgical resection. The term NSCLC encompasses the following three histologic types of neoplasm (see: Lung cancer - non-small cell):
- Adenocarcinomas that are often found in an outer area of the lung.
- Squamous cell carcinomas that is usually found in the center of the lung next to a bronchus.
- Large cell carcinomas that can occur in any part of the lung. They tend to grow and spread faster than the other two types.