Adding an immunotherapy pill to standard pre-surgery treatment of colorectal cancer patients doubled the successful outcomes in a Providence Cancer Institute phase II clinical trial, with tumors shrinking significantly or completely, allowing medical management rather than surgery.
The study, “Galunisertib plus neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a single-arm phase II trial,” was published today in The Lancet Oncology. The Lancet Oncology is a peer-reviewed international clinical oncology research journal. The trial, led by Kristina Young, M.D., Ph.D., enrolled 38 patients over four years, with 12 patients, or 32%, achieving complete response. This compares to a historical response rate of 15% with standard treatment. Lives were saved with the addition of Galunisertib, an immunotherapy pill that helped activate the patient’s immune system to fight the cancer.
Chris Parkinson noticed blood in his stool and was diagnosed with stage III colorectal cancer February 2020 at age 51. “There was such a whirlwind of activity learning about treatment options,” said Parkinson. “And when I learned about the trial I thought, why not?” Following the immunotherapy, chemotherapy and radiation, his 4.4cm tumor shrunk to the point it was barely visible. Surgery showed there was no remnant of the cancer. Parkinson is thriving today, busy with his wife, three sons and business.
Karen Wehner was six years out from her first colonoscopy when she noticed blood in her stool. Her March 2020 diagnosis was stage II colorectal cancer. She joined the clinical trial after learning about it. “Why wouldn’t I give myself every possible chance to beat this?” said Wehner. After weeks of the immunotherapy pill, radiation and oral chemotherapy, her tumor, once the size of a walnut, was not detectable. She no longer needed surgery but did undergo a series of chemo infusions to fight any unseen cancer. Wehner is currently training to run the 199-mile 2022 Hood to Coast Relay with a team of cancer survivors, which benefits research at Providence Cancer Institute.
The clinical trial was open to patients with stage II and higher rectal cancer who are slated to undergo the standard treatment of radiation and chemotherapy prior to surgery. The trial added an additional component to the pre-surgery radiation/chemotherapy regimen – immunotherapy in the form of daily pills for two weeks prior to radiation and chemotherapy, and then during that treatment as well.
Under standard protocol, patients are given radiation and chemotherapy treatments prior to surgery with the hope they will shrink the tumor slightly. Dr. Young’s research suggested adding the immunotherapy drug Galunisertib would rev the immune system and further shrink the tumors. Galunisertib was under development by Eli Lilly and Company at the time of the trial.
“Response to chemoradiation prior to surgery for rectal cancer is associated with better cancer survival – we believe the right immune therapy in this setting can improve these outcomes. Our trial showed improved outcomes in those patients who went to surgery, and high rates of organ preservation in those who were eligible for medical management,” said Dr. Young.
The success of this trial warrants further randomized study. “We are hopeful that with the many TGFbeta inhibitors in development by major pharmaceutical companies, a phase III study will develop soon,” said Dr. Young.
Advances in colorectal cancer treatments such as this research comes at a critical time as data from the past 20 years shows a significant increase in colorectal cancer diagnoses in people under the age 50. The American Cancer Society and the U.S. Preventive Services Task Force have revised their guidelines to begin colorectal cancer screening at age 45.
Colorectal cancer is the third most commonly diagnosed caner in mend and women combined in the United States, and the second most common cause of death from cancer.
Dr. Young’s trial was a continuation of her post-doctoral work on modifying the tumor microenvironment in combination with radiation to improve the outcome for patients with rectal cancer. This particular type of immunotherapy has great potential for use across many tumor types. “We are working on clinical trials in head and neck cancer, which have shown promising results in the lab,” said Dr. Young.
Providence Cancer Institute offers hundreds of active cancer clinical trials. Learn more here.
About Dr. Young
Dr. Young is a radiation oncologist with The Oregon Clinic and an Assistant Member, Tumor Microenvironment Laboratory at the Earle A. Chiles Research Institute, the research arm of Providence Cancer Institute. She is also medical director of radiation oncology at the institute.
About the Providence Colorectal Cancer Program
The Providence Colorectal Cancer Program provides screening through diagnosis, treatment and follow-up for patients with colon, rectal and anal cancer. Our multidisciplinary team extends both expertise and compassion, ensuring all patients feel well-informed about their treatment options, as well as safe and supported through every phase of their care. We also offer clinical trials, which means patients have access to the latest study treatments, including immunotherapy. In 2021, we received accreditation from the National Accreditation Program for Rectal Cancer (NAPRC). Providence Portland and Providence St. Vincent medical centers were the first in the Pacific Northwest and among the first 25 in the nation to earn this honor.