A possibility of treatment that also reaches the most critical patients: those with metastatic colorectal cancer in the most critical conditions. In fact, European Commission approval has arrived for nivolumab plus ipilimumab in the treatment of adult patients with metastatic colorectal cancer (mCRC) with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H) after previous chemotherapy. The European Commission decision is based on the results of the Phase 2 CheckMate -142 study in which the combination of nivolumab plus ipilimumab demonstrated a clinically meaningful improvement in the objective response rate (ORR) in patients with metastatic colorectal cancer ( mCRC) with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H) who had received previous treatment with fluoropyridine, oxaliplatin and irinotecan.
Metastatic colorectal cancer is an aggressive disease with a poor prognosis. With this approval, European patients with metastatic colorectal cancer with mismatch repair deficiency or high microsatellite instability will now have the first treatment based on dual immunotherapy.
The combination of nivolumab and ipilimumab is the first treatment option based on a dual immunotherapy approved in the European Union (EU) for gastrointestinal cancers. Nivolumab in combination with ipilimumab received EMA approval in first-line treatment of adult patients with advanced melanoma, in first-line treatment of adult patients with intermediate / poor-risk advanced renal cell carcinoma, in combination with two courses of chemotherapy in the first-line treatment of adult patients with metastatic non-small cell lung cancer and in the first-line treatment of adult patients with inoperable malignant pleural mesothelioma.
The CheckMate Study -142
The CheckMate -142 study included a multicenter, non-randomized, open-label cohort for the analysis of nivolumab plus ipilimumab in patients with metastatic colorectal cancer (mCRC) with mismatch repair deficiency (dMMR) or high microsatellite instability ( MSI-H) with disease progression during or after previous chemotherapy with fluoropyrimidine, oxaliplatin or irinotecan. In this combination cohort, patients received nivolumab 3 mg / kg with ipilimumab 1 mg / kg every three weeks for four doses, followed by single agent nivolumab 3 mg / kg every two weeks until disease progression, death, or toxicity. unacceptable. Results from the CheckMate -142 study with a minimum follow-up of 46.9 months showed that 64.7% of patients responded to treatment with nivolumab plus ipilimumab, with 12.6% complete responses.
What is mismatch repair deficit
This type of cancer develops in the colon or rectum, which are part of the digestive or gastrointestinal tract. Globally, colorectal cancer is the third most commonly diagnosed cancer in the world. In 2020, an estimated 1,931,000 new cases of the disease were estimated, which will be the second leading cause of cancer death among men and women overall. Mismatch repair deficiency (dMMR) occurs when proteins that repair mismatch errors in DNA replication are deficient or non-functioning, causing highly unstable microsatellite (MSI-H) tumors. About 5% of patients with metastatic colorectal cancer have the dMMR or MSI-H forms. Patients with these biomarkers are less likely to benefit from traditional chemotherapy and usually have a poor prognosis.
.