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Broad Molecular Profiling in Colorectal Cancer

Panelists:Dirk Arnold, MD, PhD, Tumor Biology Center; Fortunato Ciardiello, MD, PhD, Second University of Naples; John L. Marshall, MD, Georgetown University Hospital
Published: Friday, Jul 17, 2015



Patients with BRAF-mutated colorectal cancer (CRC) tend to have a poor response to therapy and a worse prognosis. Although it is not currently actionable, BRAF testing is typically conducted routinely for research purposes, says Fortunato Ciardiello, MD. At his practice in Germany, Dirk Arnold, MD, indicates that he commonly conducts BRAF testing, since the presence of a mutation could indicate the need for aggressive upfront treatment.

Not all patients with BRAF-mutated CRC require intensive therapy, as research continues to reveal the intricacies of the BRAF mutation, adds John Marshall, MD. Microsatellite instability (MSI) could be used to help guide the need for intensive therapy, as the presence of a BRAF mutation in a patient with MSI CRC may have less of an impact versus those with stable tumors, Marshall adds. 

These intricacies enhance the importance of molecular testing in CRC, with broad molecular profiling commonly being centralized in comprehensive cancer centers, says Ciardiello. However, the path to personalization and individualization of treatment is still a very complex issue, notes Ciardiello.

The practice of broad profiling makes treatment better but not necessarily more cost efficient, comments Arnold. For example, promising data from the phase II HERACLES trial demonstrated benefit in double inhibition of HER2 with trastuzumab and lapatinib in patients with HER2-positive metastatic CRC. In pretreated patients with primarily resistance to cetuximab or panitumumab, the objective response rate was 34.7% and the disease control rate was 78% with the dual therapy. 

In this study, HER2 amplification was found in approximately 5% of patients with wild-type KRAS exon 2 mCRC. While this potential therapy is highly efficacious for a subset of patients, it is not necessarily cost effective, since broad testing would be needed, adds Arnold. However, these dual therapies could change a patient's life, notes Ciardiello. 
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Patients with BRAF-mutated colorectal cancer (CRC) tend to have a poor response to therapy and a worse prognosis. Although it is not currently actionable, BRAF testing is typically conducted routinely for research purposes, says Fortunato Ciardiello, MD. At his practice in Germany, Dirk Arnold, MD, indicates that he commonly conducts BRAF testing, since the presence of a mutation could indicate the need for aggressive upfront treatment.

Not all patients with BRAF-mutated CRC require intensive therapy, as research continues to reveal the intricacies of the BRAF mutation, adds John Marshall, MD. Microsatellite instability (MSI) could be used to help guide the need for intensive therapy, as the presence of a BRAF mutation in a patient with MSI CRC may have less of an impact versus those with stable tumors, Marshall adds. 

These intricacies enhance the importance of molecular testing in CRC, with broad molecular profiling commonly being centralized in comprehensive cancer centers, says Ciardiello. However, the path to personalization and individualization of treatment is still a very complex issue, notes Ciardiello.

The practice of broad profiling makes treatment better but not necessarily more cost efficient, comments Arnold. For example, promising data from the phase II HERACLES trial demonstrated benefit in double inhibition of HER2 with trastuzumab and lapatinib in patients with HER2-positive metastatic CRC. In pretreated patients with primarily resistance to cetuximab or panitumumab, the objective response rate was 34.7% and the disease control rate was 78% with the dual therapy. 

In this study, HER2 amplification was found in approximately 5% of patients with wild-type KRAS exon 2 mCRC. While this potential therapy is highly efficacious for a subset of patients, it is not necessarily cost effective, since broad testing would be needed, adds Arnold. However, these dual therapies could change a patient's life, notes Ciardiello. 
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