The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the treatment of adult patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC) after prior fluoropyrimidine-based combination chemotherapy. This decision marks a significant step forward in addressing the unmet needs of patients with this specific subtype of CRC.
The recommendation is based on clinical evidence demonstrating the efficacy of the nivolumab and ipilimumab combination in patients who have progressed on or after standard chemotherapy regimens. dMMR/MSI-H CRC is characterized by a deficiency in DNA mismatch repair, leading to high levels of microsatellite instability. This genomic alteration results in increased tumor immunogenicity, making these tumors potentially more responsive to immunotherapy.
The CHMP's decision expands the therapeutic options for patients with dMMR/MSI-H metastatic CRC, who often face a poor prognosis. Current treatment strategies for advanced CRC typically involve chemotherapy, targeted therapies, and surgery where feasible. However, patients with dMMR/MSI-H tumors may not respond as well to conventional chemotherapy, highlighting the need for alternative treatment approaches.
Nivolumab and ipilimumab are immune checkpoint inhibitors that work by blocking the PD-1 and CTLA-4 pathways, respectively. By inhibiting these pathways, the drugs enhance the ability of the immune system to recognize and destroy cancer cells. The combination of nivolumab and ipilimumab has shown synergistic activity in various cancers, leading to improved clinical outcomes.
The full indications for Opdivo will now include melanoma, adjuvant treatment of melanoma, non-small cell lung cancer (NSCLC), malignant pleural mesothelioma (MPM), renal cell carcinoma (RCC), classical Hodgkin lymphoma (cHL), squamous cell cancer of the head and neck (SCCHN), urothelial carcinoma, dMMR or MSI-H CRC and oesophageal squamous cell carcinoma. Similarly, Yervoy's indications will include melanoma, RCC, NSCLC, MPM and dMMR or MSI-H CRC.
Detailed recommendations for the use of nivolumab and ipilimumab will be available in the updated summaries of product characteristics (SmPC), which will be published in the revised European public assessment reports (EPAR) after the European Commission grants a decision on these changes to the marketing authorizations.
