Nav: Home

New colorectal cancer targeted therapy combination shows promise

January 17, 2017

PORTLAND, OR - 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.

SWOG investigator Dr. Scott Kopetz will present the research Saturday, Jan. 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 cell growth.

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 protein. 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. The 106 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 4.4 months. The three-drug combination was also much more effective in controlling the disease. Study results showed that 67 percent of patients who got vemurafenib responded to treatment and their tumors stopped growing or shrank. Only 22 percent 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. About 60,000 people are diagnosed in the U.S. with metastatic colorectal cancer each year, and about 7 percent have a BRAF mutation. So each year, this could help thousands of people who have no effective course of treatment."
-end-
Along with Kopetz and Hochster, the S1406 team includes: Shannon McDonough of Fred Hutchinson Cancer Research Center; Dr. Van Karlyle Morris of MD Anderson Cancer Center; Dr. Heinz-Josef Lenz of USC Norris Comprehensive Cancer Center; Dr. Anthony Magliocco of Moffitt Cancer Center; Dr. Chloe Evelyn Atreya of UCSF Helen Diller Comprehensive Cancer Center; Dr. Luis A. Diaz of Johns Hopkins Kimmel Cancer Center; Dr. Stephen E. Wang of Kaiser Permanente and UC Davis Medical Center; Dr. Christopher Hanyoung Lieu of University of Colorado School of Medicine; Dr. S. Gail Eckhardt of University of Colorado School of Medicine; Dr. Thomas John Semrad of UC Davis Health System; Dr. Katherine Guthrie of Fred Hutchinson Cancer Research Center; and SWOG protocol coordinator Kimberly Kaberle.

The NCI funded the research through grants CA180888, CA180819, CA180820, CA180821, CA180868, CA187238. Genentech also supported the study.

SWOG is part of the National Cancer Institute's National Clinical Trials Network and the NCI Community Oncology Research Program. SWOG has over 12,000 members in 46 states and six foreign countries who design and conduct cancer clinical trials. Founded in 1956, SWOG's 1,300 trials have led to the approval of 14 cancer drugs, changed more than 100 standards of cancer care, and saved more than 2 million years of human life. Learn more at swog.org.

SWOG

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...