Initial results from the non-randomized NICHE-2 study showed that short-term neoadjuvant nivolumab (Opdivo) plus ipilimumab (Yervoy) led to pathologic responses (PRs) in nearly all patients with nonmetastatic mismatch repair (MMR)-deficient colon cancer. The findings, presented at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris, were met with applause (Abstract LBA7).
“With the data that we have shown today, and considering the relative resistance of these tumors to chemotherapy, I believe that neoadjuvant immunotherapy has a very strong potential to become standard of care for patients with [MMR-deficient] colon cancer. The future has never been brighter for this patient population,” said Myriam Chalabi, MD, lead author of the study and a medical oncologist at the Netherlands Cancer Institute in Amsterdam.
Approximately 10% to 15% of colon cancers are MMR-deficient, and one-third of these are associated with Lynch Syndrome. Unfortunately, neoadjuvant chemotherapy only leads to a pathologic response in 5% to 7% of patients with MMR-deficient colon cancer.
In the NICHE-2 study, 107 patients with nonmetastatic MMR-deficient colon cancer were treated with one dose of ipilimumab and two doses of nivolumab, followed by surgery within six weeks of registration. PR was defined half or less of the residual viable tumor (RVT) remaining and major pathologic response (MPR) as 10% or less of RVT.
At a median time from the first dose to surgery of five weeks, 99% experienced a PR and 95% had an MPR. In addition, 67% experienced a pathologic complete response. “You don’t see many waterfall plots like this. It’s striking data,” said ESMO discussant James Larkin, MD, PhD, a consultant medical oncologist at The Royal Marsden Hospital in London, referencing a chart of MPRs shown during the presentation.
None of the patients had experienced a disease recurrence at a median follow-up of 13 months. Dr. Chalabi said the three-year disease-free survival data is expected to be reported in 2023.
While the final results will not be available until next year, Sherene Loi, MD, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at Peter MacCallum Cancer Centre in Victoria, Australia, and another discussant for the ESMO session, said that these initial findings demonstrate why determining the appropriate duration of immune checkpoint inhibitors remains an important clinical question.
“We have seen in the NICHE-2 study the outstanding results of a biomarker-selected population simply with just six weeks of therapy, so clearly less is likely to be enough in these highly responsive tumors. Of course, this is important for resourcing and cost, as well as long-term adverse events,” she said.
The NICHE-2 study was funded by Bristol-Myers Squibb.
Dr. Chalabi reported relationships with Bristol Myers Squibb, MSD, and Roche.
Dr. Larkin reported relationships with Bristol Myers Squibb, Esai, Ipsen Developments, Merck Serono, Novartis, and Pfizer.
Dr. Loi reported relationships several companies, including Roche/Genentech, Novartis, and Merck.