MicroRNA-31-3p Expression is a Predictive Biomarker of Anti-EGFR Efficacy in Patients with RAS Wild-type Metastatic Colorectal Cancer

October 9th, 2018

Advanced ColoRectal Cancer (CRC) is often incurable and standard chemotherapy when combined with anti EGFR (Epidermal Growth Factor Receptor) targeted monoclonal antibodies such as VECTIBIX® (Panitumumab) and ERBITUX® (Cetuximab) as well as anti VEGF agent AVASTIN® (Bevacizumab), have demonstrated improvement in Progression Free Survival (PFS) and Overall Survival (OS). The benefit with anti EGFR agents however is only demonstrable in patients with metastatic CRC, whose tumors do not harbor RAS mutations. It is now becoming clear that among these pan RAS wild type tumors, a predictive biomarker, MiR-31-3p expression in tumors, may further determine who would benefit from Anti-EGFR targeted therapy.
In a recently published study (Clin Cancer Res 2018), tumors with Low MiR-31-3p expression benefited from ERBITUX® combination compared to AVASTIN® for PFS (HR=0.74;P=0.05), OS (HR=0.61;P<0.01) and Objective Response Rate (P<0.01). There was however no difference in outcomes among High MiR-31-3p expressors between the two treatment groups. This study suggested that only low MiR-31-3p expressing tumors among the pan RAS wild type CRC patients benefit from Anti-EGFR targeted therapies.

American Cancer Society Updates Colorectal Cancer Screening Guideline for Average Risk Adults

September 17th, 2018

The ACS recently updated Colorectal Cancer Screening Guideline using prevailing evidence as well as microsimulation modeling analyses. The new guideline does not prioritize among screening test options. This is because test preferences vary among individuals and the guidelines development committee emphasized that screening rates could be improved by endorsing the full range of tests without preference. Adults born around 1990 have twice the risk of colon cancer and four times the risk of rectal cancer compared with adults born around 1950, who have the lowest risk. In the updated guideline, screening is recommended earlier, starting at age 45 years and may be performed  with either a high-sensitivity stool-based test or a structural (visual) exam, depending on patient preference and test availability.

FDA Approves OPDIVO® for MSI-H or dMMR Metastatic Colorectal Cancer

August 15th, 2017

The FDA on July 31, 2017, granted accelerated approval to OPDIVO® (Nivolumab) for the treatment of patients 12 years and older with MisMatch Repair deficient (dMMR) and MicroSatellite Instability-High (MSI-H) metastatic ColoRectal Cancer, that has progressed following treatment with a Fluoropyrimidine, Oxaliplatin, and Irinotecan. NCCN Guidelines recommend MMR or MSI testing for all patients with a history of Colon or Rectal cancer. Patients with metastatic ColoRectal Cancer who have dMMR or MSI-H tumors are less likely to respond to conventional chemotherapy and OPDIVO® demonstrated durable responses and disease control in this heavily pretreated patient group.

Three Months of Adjuvant Therapy Adequate for Stage III Colon Cancer

July 13th, 2017

The IDEA Collaboration is a prospective, pre-planned pooled analysis of 6 concurrently conducted randomized phase III trials, which included 12,834 patients from 12 countries. They concluded that a risk-based approach has to be taken when making adjuvant chemotherapy recommendations for patients with stage III colon cancer. Three months of adjuvant chemotherapy is adequate for patients with T1-3, N1 disease. This study data was presented at 2017 ASCO Annual Meeting.

ZALTRAP® for second line treatment of metastatic CRC

April 15th, 2012

ZALTRAP® (Aflibercept) is a soluble fusion protein that is capable of binding with high affinity to pro-angiogenic factors such as all VEGF-A isoforms, VEGF-B, and PlGF. This is unlike bevacizumab, which is a monoclonal antibody that only targets all isoforms of VEGF-A.  In the VELOUR trial, second-line chemotherapy in combination with ZALTRAP® (Aflibercept) demonstrated significant improvement in the progression-free survival  as well as overall survival compared to chemotherapy alone. This benefit was seen irrespective of prior bevacizumab therapy. This data was presented at the 13th ESMO world congress.

Regorafenib improves survival in advanced CRC

April 15th, 2012

The CORRECT trial is a randomized phase III  study which demonstrated improved survival with Regorafenib, an oral multikinase inhibitor when compared to placebo, in individuals with advanced colorectal cancer, who had progressed on all available standard therapies. This important study gives a new option for individuals with advanced colorectal cancer. Additional data will be presented at ASCO 2012 meeting.

Oncoprescribe Blog: To treat or not to treat Stage II colon cancer? – Molecular Markers to the rescue

October 26th, 2010

As we understand the molecular biology of colon cancer, it is becoming clear that tumors with MisMatch Repair Deficiency (MMR-D) and high MicroSatellite Instability (MSI) tend to have a favorable prognosis and do not benefit from chemotherapy and on the contrary, 5-FU based chemotherapy may potentially result in a detrimental effect. The Oncotype DX colon cancer 12 gene assay is a valuable tool that can provide additional information in the decision making process.

Oncoprescribe Blog: Will BRAF trump KRAS testing in Metastatic Colon Cancer?

September 6th, 2010

Testing for KRAS mutations is presently the standard of care prior to treatment with anti EGFR monoclonal antibodies such as cetuximab and panitumumab, as KRAS mutant colorectal tumors do not respond to anti EGFR monoclonal antibodies. However it is becoming clear that BRAF which is involved in intracellular signaling and cell growth and a principal downstream mediator of KRAS, when mutated resulted in shorter progression free survival and overall survival regardless of KRAS status. Targeted therapy may be taking a turn for the better making treatment more personalized.