Neoadjuvant Immunotherapy with Nivolumab and Ipilimumab Shows Promise for Mismatch Repair–Deficient Colon Cancer
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on July 3rd, 2024
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Defects in the mismatch repair cellular machinery are present in 15% of nonmetastatic colon cancer cases. Currently, these patients are treated similarly to those with competent mismatch repair mechanisms, receiving adjuvant chemotherapy with fluorouracil plus oxaliplatin after surgery. Recent data, however, have shown that this approach has limited efficacy. As a result, a study was conducted to evaluate the potential of using neoadjuvant immunotherapy, specifically nivolumab plus ipilimumab, in colon cancer patients with mismatch repair deficiency.
The phase 2 clinical study involved 115 patients, with a median age of 60 years, diagnosed with resectable colon adenocarcinoma. Tumor biopsies underwent immunohistochemical staining to assess the competency of mismatch repair proteins such as MLH1, PMS2, MSH2, and MSH6. Participants received a regimen of neoadjuvant immunotherapy with nivolumab and ipilimumab six weeks before resection surgery. Nivolumab was administered intravenously in two doses: the first dose of 3 mg per kilogram of body weight on day 1, and the second dose on day 15. Ipilimumab was given in a single dose of 1 mg per kilogram of body weight on day 1. Post-surgery, histological analysis of the resected specimens revealed that 68% of the cohort had no residual viable tumor, 95% had less than 10% viable tumor remaining, and 98% had less than 50% residual viable tumor. Over a median follow-up of 26.2 months, none of the patients experienced disease recurrence. From the existing literature, the researchers noted that the neoadjuvant chemotherapy is too ineffective when compared to immunotherapy, making a randomized control trial ethically questionable.
The phase 2 clinical study involved 115 patients, with a median age of 60 years, diagnosed with resectable colon adenocarcinoma. Tumor biopsies underwent immunohistochemical staining to assess the competency of mismatch repair proteins such as MLH1, PMS2, MSH2, and MSH6. Participants received a regimen of neoadjuvant immunotherapy with nivolumab and ipilimumab six weeks before resection surgery. Nivolumab was administered intravenously in two doses: the first dose of 3 mg per kilogram of body weight on day 1, and the second dose on day 15. Ipilimumab was given in a single dose of 1 mg per kilogram of body weight on day 1. Post-surgery, histological analysis of the resected specimens revealed that 68% of the cohort had no residual viable tumor, 95% had less than 10% viable tumor remaining, and 98% had less than 50% residual viable tumor. Over a median follow-up of 26.2 months, none of the patients experienced disease recurrence. From the existing literature, the researchers noted that the neoadjuvant chemotherapy is too ineffective when compared to immunotherapy, making a randomized control trial ethically questionable.