HER2 amplification as a negative predictive biomarker for anti-epidermal growth factor receptor antibody therapy in metastatic colorectal cancer.

Raghav, Kanwal; Overman, Michael J.; Yu, Ruoxi; Meric‐Bernstam, Funda; Menter, David G.; Kee, Bryan K.; Murányi, Andrea; Singh, Shalini; Routbort, Mark J.; Chen, Ken; Shaw, Kenna; Shanmugam, Kandavel; Maru, Dipen M.; Fakih, Marwan; Kopetz, Scott

doi:10.1200/jco.2016.34.15_suppl.3517

Cited by 73 publications

(58 citation statements)

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“…HER2 is rarely overexpressed in CRC (approximately 3% overall), but the prevalence is higher in RAS/BRAF wild-type tumors (reported at 5%-14%). 177,178 Specific molecular diagnostic methods have been proposed for HER2 testing in CRC, 179 and various therapeutic approaches are being tested in patients with tumors that have HER2 overexpression (eg, trastuzumab plus lapatinib, trastuzumab plus pertuzumab). 177,180 These approaches are currently considered investigational, and enrollment in a clinical trial is encouraged.…”

Section: The Role Of Kras Nras and Braf Statusmentioning

confidence: 99%

“…181 However, initial results indicate HER2 overexpression may be predictive of resistance to EGFR-targeting monoclonal antibodies. 178,182 For example, in a cohort of 97 patients with RAS/BRAF wild-type metastatic CRC, median PFS on first-line therapy without an EGFR inhibitor was similar regardless of HER2 status. 178 However, in second-line therapy with an EGFR inhibitor, the PFS was significantly shorter in those with HER2 amplification compared with those without (2.9 vs 8.1 months; HR, 5.0; P<.0001).…”

Section: The Role Of Kras Nras and Braf Statusmentioning

confidence: 99%

“…178,182 For example, in a cohort of 97 patients with RAS/BRAF wild-type metastatic CRC, median PFS on first-line therapy without an EGFR inhibitor was similar regardless of HER2 status. 178 However, in second-line therapy with an EGFR inhibitor, the PFS was significantly shorter in those with HER2 amplification compared with those without (2.9 vs 8.1 months; HR, 5.0; P<.0001). Larger confirmatory studies are needed, and the panel does not recommend HER2 testing for prognostication or treatment planning at this time.…”

Section: The Role Of Kras Nras and Braf Statusmentioning

confidence: 99%

See 2 more Smart Citations

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

Benson¹,

Venook²,

Cederquist³

et al. 2017

J Natl Compr Canc Netw

749

515

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OverviewColorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. In 2016, an estimated 95,270 new cases of colon cancer and approximately 39,220 cases of rectal cancer will occur. During the same year, an estimated 49,190 people will die of colon and rectal cancer combined. AbstractThis portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions. J Natl Compr Canc Netw 2017;15(3): 370-398 NCCN Categories of Evidence and ConsensusCategory 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. These guidelines are also available on the Internet. For the latest update, visit NCCN.org.

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Section: The Role Of Kras Nras and Braf Statusmentioning

confidence: 99%

Section: The Role Of Kras Nras and Braf Statusmentioning

confidence: 99%

Section: The Role Of Kras Nras and Braf Statusmentioning

confidence: 99%

See 1 more Smart Citation

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

Benson¹,

Venook²,

Cederquist³

et al. 2017

J Natl Compr Canc Netw

749

515

View full text Add to dashboard Cite

show abstract

“…HER2 amplification has been seen in about 5% of KRAS wild-type cancers. In a limited sample, patients who have this amplification had significantly inferior PFS on anti EGFR therapy (2.9 vs. 8.1 mo) (59). More studies are necessary to confirm these findings, but the mechanism is biologically plausible.…”

Section: Amplification Of Her2mentioning

confidence: 96%

Primary and acquired resistance to biologic therapies in gastrointestinal cancers

Lubner

Uboha

Deming

2017

J. Gastrointest. Oncol.

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Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care. However, responses have not been as durable nor as robust as once hoped. Mechanisms of resistance for each of these biologic compounds have been hypothesized and are in the process of being better elucidated. This review will approach the innate and acquired mechanisms of resistance of the above compounds.Additionally, we will explore some ongoing clinical trials to capitalize on the mechanisms of resistance in the hopes of retaining the promise of targeting these pathways. Resistance to EGFR inhibitors: primaryAs many tumors of the gastrointestinal tract arise from epithelial origins, the attractiveness of treating with therapies blocking EGFR is readily evident. A series of colon cancer trials have shown, improvements in RRs and OS, particularly in populations without mutations in EGFR and/or downstream effectors, which are described in the next section. In most other GI cancers, however, blocking EGFR has not demonstrated clinically relevant improvements in outcome (2-4). New strategies to investigate anti-EGFR therapy in other tumor types are focusing on selecting for patients whose tumors overexpress EGFR, or do not harbor deleterious mutations (ENRICH study, NCT 01813253) (5). KRAS/NRASKRAS and NRAS belong to the family of RAS oncogenes.

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“…Other major benefits of NGS will be discussed later when we address the roll of multiplex panels in mCRC. (80). Furthermore, these patients can derive benefit from dual-anti-HER2 inhibition using trastuzumab in combination with lapatinib (HERACLES study) or trastuzumab and pertuzumab (My Pathway study) and should be referred for clinical trials assessing HER-2 directed therapy (81-83).…”

Section: Next Generation Sequencing (Ngs)mentioning

confidence: 99%

Current companion diagnostics in advanced colorectal cancer; getting a bigger and better piece of the pie

Loree

Kopetz

Raghav

2017

J. Gastrointest. Oncol.

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While the treatment of colorectal cancer continues to rely heavily on conventional cytotoxic therapy, an increasing number of targeted agents are under development. Many of these treatments require companion diagnostic tests in order to define an appropriate population that will derive benefit. In addition, a growing number of biomarkers provide prognostic information about a patient's malignancy. As we learn more about these biomarkers and their assays, selecting the appropriate companion diagnostic becomes increasingly important. In the case of many biomarkers, there are numerous assays which could provide the same information to a treating physician, however each assay has strengths and weaknesses. Institutions must balance cost, assay sensitivity, turn-around time, and labor resources when selecting which assay to offer. In this review we will discuss the current state of companion diagnostics available in metastatic colorectal cancer and explore emerging biomarkers and their assays. We will focus on KRAS, BRAF, HER2, and PIK3CA testing, as well as microsatellite stability assessment and multigene panels.

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HER2 amplification as a negative predictive biomarker for anti-epidermal growth factor receptor antibody therapy in metastatic colorectal cancer.

Cited by 73 publications

References 0 publications

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

Primary and acquired resistance to biologic therapies in gastrointestinal cancers

Current companion diagnostics in advanced colorectal cancer; getting a bigger and better piece of the pie

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