About 60,000 people are
diagnosed in the United States with metastatic colorectal cancer each year, and
about 7% have a BRAF mutation.
New SWOG study results show significantly better outcomes for
patients with a treatment-resistant form of metastatic colorectal cancer
when the BRAF inhibitor vemurafenib is added to a standard treatment.
The findings, for the first time, point at an effective treatment for
this deadly type of cancer.
‘Patients with a treatment-resistant form of metastatic colorectal cancer have better outcomes when BRAF inhibitor vemurafenib is added to a standard treatment.’
SWOG investigator Dr. Scott Kopetz will present the research
Saturday, January 21 at the 2107 Gastrointestinal Cancers Symposium in San
Francisco. The symposium showcases the latest science and is sponsored
by the field's leading specialty societies: the American
Gastroenterological Association (AGA) Institute, the American Society of
Clinical Oncology (ASCO), the American Society for Radiation Oncology
(ASTRO), and the Society of Surgical Oncology (SSO).
An associate professor at the University of Texas MD Anderson Cancer
Center and a member of SWOG's gastrointestinal research committee,
Kopetz has spent nearly a decade studying BRAF-mutant metastatic
colorectal cancer - how it works and how to shut it down. Mutation of
the BRAF gene is implicated in many cancers and works by fueling cancer
Kopetz became interested in therapies to target BRAF mutations years
ago, and conducted early research to determine the safety and efficacy
of vemurafenib, an inhibitor that targets the mutated form of the BRAF
The U.S. Food and Drug Administration in 2011 approved its use
for the treatment of patients with inoperable or metastatic melanoma
with a BRAF V600E mutation, and Genentech now sells it under the name
Zelboraf. However, studies testing vemurafenib alone in metastatic
colorectal cancer patients failed to show a benefit. But what if
vemurafenib was combined with not one but two other cancer drugs?
Kopetz tested the idea in an earlier trial and, because of promising
results, launched a randomized study, S1406, managed by SWOG, a group
of cancer clinical trial specialists funded by the National Cancer
Institute (NCI) under its National Clinical Trials network.
patients enrolled in S1406 had BRAF V600E metastatic colorectal cancer, a
late-stage condition in which the cancer has spread to other organs and
resisted prior treatment. Roughly half the patients received an
investigational regimen consisting of vemurafenib with the combination
of irinotecan, a traditional chemotherapy drug, and cetuximab, a therapy
targeting the epidermal growth factor receptor (EGFR), which can cause
cancer cells to grow.
Other patients received irinotecan and cetuximab
alone, a standard treatment for metastatic colorectal cancer. If cancer
progressed for patients getting standard treatment, they were given the
option to try the vemurafenib regimen.
Results showed that patients who got the treatment with vemurafenib
had better progression-free survival rates. Patients who got the typical
two-drug combination saw their cancer grow or spread, on average, two
months after beginning treatment. That length of time more than doubled
for patients who also got vemurafenib, with a median progression time of
The three-drug combination was also much more effective in
controlling the disease. Study results showed that 67% of
patients who got vemurafenib responded to treatment and their tumors
stopped growing or shrank. Only 22% of patients who got standard
treatment had this response.
"This looks like the one-two punch this cancer needs," Kopetz said.
"Vemurafenib inhibits the action of the mutant BRAF gene. But that can
activate the EFGR cancer signaling pathway. Cetuximab shuts those
signals down. So this combination hits not one cancer pathway, but two."
Dr. Howard Hochster, associate director of the Yale Cancer Center,
chair of SWOG's gastrointestinal research committee, and senior member
of the S1406 study team, said in the coming months, researchers will
analyze overall survival data - data that can show whether the
vemurafenib combination helps people live longer.
"If those findings are positive, this will set a new standard of
care," Hochster said. "That's big news. So each year, this could help
thousands of people who have no effective course of treatment."