Response DX: Lung – pro

ResponseDX Lung is actually a panel of predictive markers. They include markers that are generally accepted, for examlpl KRAS and EGFR as well as markers that are still considered experimental for decision making, such as TS, ERCC1, BRAF, EML4-ALK, RRM1.

A little clinical information about these tests based on the information from the ResponseGenetics website: The epidermal growth factor receptor (EGFR; ErbB-1; HER1) is a critical part of the signal transduction pathway that controls cell growth and is often over-expressed (amplified) in tumors. A higher number of gene copies has been shown to correlate with increased response of non-small cell lung cancer (NSCLC) to the EGFR-directed small-molecule TKI’s. NCCN guidelines mentions this test. In four independent clinical correlative studies involving 134 NSCLC patients, those with KRAS-mutants showed poorer clinical outcomes to treatment with EGFR-directed TKI’s, either in terms of no response or no survival benefit.

KRAS is mentioned in the FDA indcation for Erlotinib. Retrospective subset analyses of metastatic or advanced colorectal cancer trials have not shown a treatment benefit for Erbitux (cetuximab) in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Erbitux (cetuximab) is not recommended for the treatment of colorectal cancer with these mutations.

A recent clinical trial showed that lower TS expression was associated with better response of NSCLC to neoadjuvant chemotherapy with gemcitabine and pemetrexed. The results of both of the above studies suggest that high ERCC1 patients treated with non-platinum therapy may also achieve a better result than that seen in non-selected groups of patients.

ALK inhibitors have entered clinical development and remarkably clinical efficacy has been observed in NSCLC patients harboring EML4-ALK translocations A recent feasibility trial was performed in which therapies were assigned taking into account both RRM1 and ERCC1 gene expressions. Patients with low RRM1 were given either gemcitabine/carboplatin if their ERCC1 levels were low, or gemcitabine/docetaxel if their ERCC1 levels were high; patients with high RRM1 were given docetaxel/carboplatin if they had low ERCC1 and docetaxel/vinorelbine if they had high ERCC1. All four selected arms showed response rates of around 44%, compared to about 25% in historical controls of unselected patients.

A recent study showed that a V660E mutation in BRAF, a gene that is downstream of KRAS in same cell cycle signaling pathway, identified a further set of 12-15% of metastatic colorectal cancer patients with wild-type KRAS who would fail to respond to TKI’s.1 Both a wild-type BRAF gene as well as a wild-type KRAS gene are necessary for response.

Is the entire panel med. necessaryl? Since the EGRF and KRAS on the panel are medically necessary, I consider the entire test medically necessary. Insureres  may consider negotating the total price for the panel based on the two medically necessary components., colon cancer

prescribing information, Erlotinib

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