A symposium presented at the American Association for Cancer Research Annual Meeting 2016 offers updated results on the ongoing phase 1b clinical trial of anti-PDL1 immunotherapy atezolizumab in advanced stage colorectal cancer patients. Treated at the University of Colorado Cancer Center, one of the earliest trial participants is Rodney Bearfoot, who remains on trial with stable disease three years after being diagnosed with stage 4 colon cancer.
"We believe that tumor shrinkage isn't the only measure of successful cancer immunotherapy. In this case and others, the long term control of advanced colorectal cancer is a goal unto itself," says S. Gail Eckhardt, MD, FASCO, associate director for translational research at the University of Colorado Cancer Center.
The drug works by reinitiating the immune system's ability to recognize and destroy tumor tissue. Specifically, atezolizumab is one in a promising class of drugs known as PDL1 inhibitors. When the PDL1 receptor on a tumor cell's surface binds the protein PD-1, the interaction results in signaling that protects the cell against destruction by the immune system's T lymphocytes. Atezolizumab binds to PDL1 receptors, blocking the receptors' ability to bind PD-1 and thus reopening cells to immune system attack.
Atezolizumab was granted Breakthrough Therapy Designation by the FDA for the treatment of metastatic bladder cancer. The drug is also showing promising early results in clinical trials of breast cancer, non-small cell lung cancer, renal cell carcinoma and melanoma.
The current study reports results of 23 patients with metastatic colorectal cancer. Fifty-two percent of patients responded to treatment, which also included the chemotherapy FOLFOX and the anti-VEGF therapy bevacizumab. Median progression free survival was 14.1 months with a median duration of response of 11.4 months.
"I've been on the study so long, they went ahead and named it atezolizumab," says Bearfoot. "I had really hoped that they would have named the drug something that I could have pronounced!"
Bearfoot was diagnosed with colon cancer in 2008 and was treated with chemotherapy. In 2010 metastases were found in his lungs. At that point, Bearfoot became a patient with Eckhardt at the CU Cancer Center and underwent further chemotherapies that controlled his disease until 2013. Unfortunately, the tumor again started to progress and Bearfoot became eligible for the phase 1b clinical trial of atezolizumab.
"It's been more than three years and he is still on study," says Eckhardt.
"It amazes me that I have been blessed with such good fortune to be six years away from my stage 4 diagnosis," Bearfoot says. "I retired shortly after that diagnosis and have been working on all the items I put off during my working career."
Eckhardt describes another study participant who, with stage 4 colorectal cancer in his early 30s, continues to work fulltime. "You would never know he has cancer," Eckhardt says.
While many other types of cancer including lung, renal and melanoma have responded dramatically to immune therapies, several gastrointestinal cancers have been resistant, potentially decreasing interest in continued testing of immunotherapies in this population.
However, Eckhardt points out that, "It is well established in colorectal cancer that many regimens that offer overall survival benefit lead to disease stability and not shrinkage. While fewer patients have experienced tumor shrinkage, many of us that specialize in GI cancer are quite impressed with how long CRC patients have been on this study and are working together to move ahead with research in this area. This study update provides potential biomarkers that might help identify CRC patients that will benefit from immunotherapy, like Mr. Bearfoot."