Benjamin A. Weinberg, MD
Throughout the oncology landscape we are trying to incorporate immunotherapy into the treatment paradigm, and while this has been very successful in certain types of cancer (e.g. melanoma, lung cancer, and kidney cancer), colorectal cancer has been mostly left behind by the immunotherapy revolution to date. In a phase II single-arm study out of China, Lin and coworkers added camrelizumab, an anti-PD-1 monoclonal antibody, to neoadjuvant CAPOX chemotherapy following short-course radiation for patients with locally advanced rectal cancer. Of 27 evaluable patients, 13 had a pathological complete response (pCR, 48.1%), all but one of whom were mismatch repair proficient and unlikely to respond to immunotherapy. This small study laid the groundwork for an ongoing, randomized phase III study which is designed to demonstrate a significant increase in the pCR rate compared to standard neoadjuvant long-course chemoradiation and chemotherapy.
Finally, there has been excitement in the advanced setting of adding regorafenib, an oral poly-tyrosine kinase inhibitor, to immune checkpoint inhibitors for patients with mismatch repair proficient disease. Japanese data suggested a benefit from this combination which has not been fully borne out in the American experience. Yang and coauthors retrospectively analyzed the experience of regorafenib plus immune checkpoint inhibitors in mismatch repair proficient metastatic colorectal cancer patients at 14 Chinese medical centers and determined that the objective response rate in 82 patients was only 5% with a 45% stable disease rate. However, the median duration of disease control (stable disease or better) was 6.3 months which is clinically meaningful in this population. Moreover, 65% of patients have liver metastases which have proven to be more refractory to this combination in the American data. While we await more prospective studies of this combination, we continue to hold out hope that it may be a novel therapeutic option which is so desperately needed for patients with metastatic colorectal cancer.