Presurgical Opdivo-Yervoy Combo Has ‘Very Strong Potential’ to Be Standard of Care for Subgroup of Patients With Colon Cancer

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None of the more than 100 evaluable patients with mismatch repair deficient colon cancer have experienced disease recurrence after treatment with presurgical Opdivo plus Yervoy, according to study results.

Almost every patient with mismatch repair-deficient colon cancer enrolled onto a multicenter clinical trial achieved some type of response when treated with the neoadjuvant combination of Opdivo (nivolumab) and Yervoy (ipilimumab), according to recently presented findings.

The data — which were unveiled at the 2022 European Society of Medical Oncology Congress — also demonstrated that 98% of the 112 patients enrolled onto the trial received surgery within six weeks of starting treatment.

According to the National Cancer Institute, neoadjuvant therapy is an initial treatment that is given to patients to shrink their tumor before they undergo surgery.

Here, the investigators launched the NICHE-2 trial after observing a group of 32 patients with nonmetastatic, mismatch repair-deficient colon cancer achieve a 100% pathologic response (the disappearance of some or all traces of cancer in tissue samples removed during surgery) rate when treated with an immune checkpoint inhibitor. The same findings showed that of the responses to the treatment, 60% of patients derived a complete response, meaning all signs of disease were gone.

In the NICHE-2 trial, 112 patients were administered Opdivo plus Yervoy during their first cycle of treatment. Then, the patients received only Opdivo two weeks later followed by surgery within six weeks of enrolling onto the trial. Assessing the three-year disease-free survival (time after treatment has ended that a patient remains alive without signs or symptoms of their cancer) rate and safety of the neoadjuvant combination of Opdivo and Yervoy were the main goals of the study.

The authors also aimed to investigate the major pathological response rate, as well as the complete pathological response rate. A major pathologic response was defined as 10% or less residual tumor remaining following the completion of neoadjuvant treatment.

The findings from the NICHE-2 trial showed that treatment with Opdivo plus Yervoy for four weeks was associated with a major pathologic response rate of 95%.

This outcome, according to one of the study authors, is a major improvement over what has been seen in the past for these patients.

“This stands in stark contrast to data from neoadjuvant chemotherapy in this same patient population (that had) only 7% pathologic responses,” Dr. Myriam Chalabi, a medical oncologist at the Netherlands Cancer Institute in Amsterdam, said in her presentation of the data.

Additionally, 67% of patients demonstrated pathologic complete responses and none have had a disease recurrence as of the last evaluation of the data. The presurgical treatment with Opdivo plus Yervoy was also well tolerated, with investigators observing only 4% serious or severe immune-related side effects.

Immunotherapy helps boost a person's immune system to help the body find and destroy cancer cells, according to the American Society of Clinical Oncology. Since immunotherapy activates the immune system, it can cause inflammation in any of the organs within the body, which can lead to complications called immune-related side effects.

The median time from the first treatment with the combination of Opdivo and Yervoy to surgery was 5.4 weeks. The investigators noted that there were no new safety signals but explained that 21% of patients had a surgery-related side effect of any severity. Thirteen percent of those side effects were serious or worse.

The investigators observed a major pathologic response in 102 patients, and a pathologic complete response in 72 patients following neoadjuvant treatment with Opdivo plus Yervoy.

Overall, 61% of the patient population experienced an immune-related side effect of any severity. However, only two patients had an immune-related side effect that lead to a more than two week delay in surgery. The most common mild to moderate side effects included infusion reactions, dry mouth, over- or underactive thyroid function, fatigue and flu-like symptoms.

The findings from the three-year disease-free survival analysis are expected to be available next year. Chalabi noted that future studies may observe organ-sparing approaches for patients with mismatch repair-deficient colon cancer. An organ-sparing treatment approach aims to avoid invasive surgery and preserve the function of the affected organ.

“I believe that neoadjuvant immunotherapy has a very strong potential to become standard of care for patients with (mismatch repair deficient) colon cancer,” Chalabi concluded. “The future has never been brighter for this patient population, and for that, I urge the pharmaceutical companies to please strive for registration of neoadjuvant immunotherapy.”

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