MedicalResearch.com Interview with:
Dr. Van K. Morris, MD
Assistant Professor, GI Medical Oncology
The University of Texas MD Anderson Cancer Center
MedicalResearch.com: What is the background for this study?
Dr. Morris: Anal cancer is a very rare cancer and accounts for approximately 2% of all gastrointestinal malignancies. Currently, there is no accepted standard of care for patients with metastatic disease, which raises challenges for oncologist who may not have extensive experience caring for patients with metastatic anal cancer given that there are not accepted agents to treat with. This clinical trial was the first clinical trial ever conducted for patients with stage IV disease who had received prior chemotherapy in the past.
Given the well-known association with human papilloma virus (HPV) and the development of anal cancer, we were interested in the use of immunotherapy drugs as a new possible way to awaken the immune system to attack this tumor, especially as there may be viral components in the tumor cells which the immune system could potentially recognize. Nivolumab is an immunotherapy drug which has shown activity in other solid tumors like melanoma, kidney cancer, non-small cell lung cancer, and bladder cancer.
MedicalResearch.com: What are the main findings?
Dr. Morris: Here, we report the findings from the patients who were treated at M.D. Anderson. There were patients who had good responses to this drug, and this week we are sharing our findings in which we compared the now sees of tumor biopsies between patients who responded to nivolumab and those who did not. What we found very striking was that, prior to any treatment, the patients who responded had higher levels of T cells present within their tumor and that they also had higher levels of proteins in the PD–1: PD–L1 axis relative to the nonresponding patients. Consideration of both PD–1 and PD–L1 expression on cells from the tumor biopsy were important in identifying the patients who responded. Additionally, there were higher levels of proteins like LAG–3 and TIM-3 in the responding patients, a finding which also supports the notion that activated T cells at baseline may be associated with a positive response to nivolumab.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Morris: Complete clinical results for this entire trial which was conducted through the NCI/ETCTN network at 11 institutions in the United States will be reported at ASCO and at GI ESMO later this year. Our results here provide early indication of the importance of active T cells at baseline as well as the continued importance of the PD–1: PD–L1 axis as a possible positive predictive marker for response to nivolumab. Given that there is no accepted standard of care for this disease, we continue to recommend that patients with metastatic anal cancer seek available clinical trials for new possible therapeutic options.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Morris: These findings will need to be validated in larger cohorts of patients with metastatic anal cancer, but do provide some indication initially as to the importance of the presence of active T cells as a sign for response to immune checkpoint agents for this disease. It will also be interesting to look at this trend for other HPV associated malignancies given that anal cancer is not the only cancer associated with HPV infection.
MedicalResearch.com: Is there anything else you would like to add?
Dr. Morris: We would like to think the HPV and Anal Cancer Foundation, the HPV Moonshot at M.D. Anderson, the E. B. Anal cancer fund, and an anonymous philanthropic donor for assistance with funding.
April 2016 AACR abstract:
NCI#9673 phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal: Immunologic correlates of response