Patients with localized colon cancer may benefit from a short course of neoadjuvant immunotherapy, according to findings from the exploratory phase II NICHE study published by Myriam Chalabi, MD, and colleagues in Nature Medicine.
Myriam Chalabi, MD
Study Results
Forty patients with two colon cancer subtypes—either mismatch repair (MMR)-deficient (dMMR) or MMR-proficient (pMMR)—took part in the NICHE study. Patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib.
Twenty patients had tumors that demonstrated microsatellite instability (MSI). Of all patients with nonmetastatic colon cancer, 15% have this type—and the therapy was effective in all 20 patients. “A good response rate was [in] the cards in this group,” said Dr. Chalabi. “But a 100% rate is unprecedented.”
“A good response rate was [in] the cards in this group...but a 100% rate is unprecedented.”— Myriam Chalabi, MD
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The remaining 20 patients in the NICHE study had microsatellite-stable (MSS) tumors. Researchers found that 25% of this group of patients also responded well.
The team looked for an explanation of this high response rate in the MSS group in the lab. “We looked at all the usual suspects, but they weren't the cause,” said Dr. Chalabi. “We didn't see the same predictive factors as in melanoma, for instance. But in the end, we did find a new biomarker. If that proves to be predictive in follow-up studies, it could provide a simple way of identifying patients with MSS tumors who could benefit from immunotherapy.”
All patients in the study underwent radical resection after being treated with immunotherapy, with no delays in surgery. Pathologic response was observed in 20 of 20 patients (100%, 95% confidence interval [CI] = 86%–100%) with dMMR tumors, with 19 major pathologic responses (≤ 10% residual viable tumor) and 12 pathologic complete responses. In patients with pMMR tumors, 4 of 15 (27%, 95% CI = 8%–55%) showed pathologic responses, with three major pathologic responses and one partial response reported. CD8–positive PD-1–positive T-cell infiltration was predictive of response in pMMR tumors.
The NICHE study will continue, and the number of patients will be increased. They will be monitored for at least 3 years to see whether they remain disease-free. “Only then can the new therapy be considered as a standard treatment,” said Dr. Chalabi.
The study authors concluded, “These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data.”
Disclosure: For full disclosures of the study authors, visit nature.com.
