Since 1956, SWOG investigators have changed oncology practice more than 100 times. At the 2018 Gastrointestinal Cancers Symposium last week, Dr. Scott Kopetz and the S1406 team did it again.

On January 18, the National Comprehensive Cancer Network (NCCN) released by email its clinical practice guidelines for colorectal cancer. Dr. Kopetz, a longtime SWOG member from the MD Anderson Cancer Center, was at the symposium and scrolled through the giant PDF. And there it was: Patients with metastatic CRC with tumors harboring a BRAF mutation, who have progressed on prior therapy, should be treated with the BRAF inhibitor vemurafenib added to the standard chemotherapy regimen of irinotecan and cetuximab.

At the 2017 Gastrointestinal Cancers Symposium – just the year before – Kopetz had presented the SWOG study results showing the significant benefits of using vemurafenib when added to chemotherapy in this population of patients. The S1406 findings for the first time pointed to an effective targeted treatment for this deadly cancer subtype. The findings were also the subject of a SWOG press release, which you can read here.

The S1406 story is a major success for SWOG – in many ways. The development arc of this drug was relatively short. Kopetz first tested vemurafenib in 2008 in a Phase I safety trial. Now, it’s standard of care. This is particularly astounding given the fact that BRAF-mutant metastatic colorectal cancer is uncommon, affecting just 8 percent of the colorectal cancer population. Testing treatments for hard-to-find  cancers isn’t easy – yet Kopetz and his team broke every patient accrual goal they set – proof that SWOG and other National Cancer Institute funded groups can study rare cancers effectively.

S1406 is also notable because Kopetz and his team were the first to use patient derived xenografts in an NCI National Clinical Trials Network study. They created PDX models through our partners at The Jackson Laboratory. They’re still using the models to better understand mechanisms of resistance to the vemurafenib, irinotecan, and cetuximab regimen. 

SWOG GI committee chair Dr. Howard Hochster, S1406 translational medicine lead Dr. Heinz-Josef Lenz, and SWOG TM Vice Chair Dr. Lee Ellis, will all tell you S1406 was an exceptional example of translating basic science findings from the lab to the clinic. It is proof positive of the value of our translational medicine partnerships.

Our recent NCI grant application featured our ability to leverage federal funds. This is a perfect example of why doing so is important. Kopetz and his team got the money for this translational medicine component to their trial from our Hope Foundation. Hope granted Kopetz and his team an Impact Award in 2014 to make the PDX models. This funding, he said, was essential to the speed and success of S1406.

“The Hope grant allowed us to think more ambitiously about the questions we were asking and to take the science to a deeper level,” he said. “We will continue to advance our understanding of the biology of this type of cancer, as well as study the clinical efficacy of a new treatment for it. We hope to use these models to inform the next generation of NCI trials.”

This is an incredibly satisfying story. My deepest congratulations to Drs. Kopetz, Hochster, and Lenz, as well as the entire S1406 team.
 

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Mar 8, 2024
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