George Coukos, MD, PhD ©Credit UNIL Félix Imhof

George Coukos, MD, PhD, Director of the Department of Oncology at the University Hospitals of Canton Vaud and Director of the Lausanne branch of the Ludwig Institute for Cancer Research at the University of Lausanne in Switzerland, was the invited discussant of the NICHE study at the European Society for Medical Oncology (ESMO) 2018 Congress. Dr. Coukos had high praise for this study of “real-life” patients: “This is one of the most important reports at the ESMO 2018 Congress,” he commented, basing his praise on the 100% pathologic response rate, which he called “stunning, absolutely astonishing.”

Neoadjuvant therapy in mismatch repair (MMR)-deficient colon cancer is taking advantage of the immunoreactivity of this subset of colon tumors, their innate susceptibility to checkpoint inhibition, and the fact that these characteristics are enhanced in the early stages of the disease. “There is a heterogeneity during the metastatic process—an evolutionary interplay between the immune system and tumor cells that often leads to a loss of immune activation. It makes sense to treat early,” he pointed out. “So the rationale for this study was well established. Primary colon tumors can be more immunoreactive and a better target for immunotherapy.”

‘Stunning’ Pathologic Response

Very important, according to Dr. Coukos, was the observation that distal immunity could also be mobilized through neoadjuvant immunotherapy. “We saw a dramatic infiltration of T cells and an absolutely stunning pathologic response in the course of just 2 to 4 weeks. A reduced dose of nivolumab (Opdivo) and a single dose of ipilimu-mab (Yervoy) eliminated all tumor cells.”

The treatment was well tolerated, and there were no undue surgical delays or complications. This might be the result of lower doses of the drugs or a very short treatment duration, he said, but it’s reassuring that the standard of care was not disrupted.

There is a take-home message for MMR-proficient tumors as well, he added. “There is embedded immunity in many of these tumors, and that was mobilized by this treatment, but it was not sufficient to produce a clinical or pathologic response. This is validating that something is happening—we just need more of it. This is an important area for future investigation.” ■

DISCLOSURE: Dr. Coukos has served as an advisor/consultant/speaker for NextCure, Geneos Therapeutics, Roche, Genentech, AstraZeneca, and Bristol-Myers Squibb and has received grants from Celgene, Boehringer Ingelheim, and Bristol-Myers Squibb.