The National Institute for Health and Care Excellence (NICE) has issued a Final Appraisal Document (FAD) recommending the combination of Opdivo® (nivolumab) plus Yervoy® (ipilimumab) for advanced bowel cancer patients with the rare MSI-H/dMMR mutation, after they have previously failed fluoropyrimidine-based chemotherapy.
This is the first immunotherapy combination approved in the UK for this patient group, who have a form of advanced bowel cancer characterised by rare gene mutations known as high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR), which affect how the cancer grows.[2,3,4]
There is a high unmet need in bowel cancer patients whose tumours exhibit the MSI-H/dMMR mutation, which is associated with a poor prognosis and limited treatment options.
The NICE recommendation is based on data from the ongoing Phase II Checkmate-142 study, which showed that the combination of nivolumab plus ipilimumab can potentially offer long progression-free survival (PFS) and overall survival (OS). An objective response rate of 65% after a follow up period of 51 months was seen with the combination treatment. The decision from NICE offers a new treatment option for patients with bowel cancer after chemotherapy has failed, for whom there are currently limited treatment options.
Genevieve Edwards, Chief Executive at Bowel Cancer UK said: “Advanced bowel cancer with the rare MSI-H/dMMR mutation can be difficult to treat. If chemotherapy fails then this patient population has had limited treatment options, so we welcome the NICE decision to make this combination of nivolumab with ipilimumab available to them.”
Dr Hubert Bland, Executive Medical Director UK and Ireland, Bristol Myers Squibb said: “At Bristol Myers Squibb we are committed to bringing our innovative medicines to patients across the UK and Ireland. We are grateful to the hospitals and patients involved in the trials that have helped bring this immunotherapy combination to patients with advanced bowel cancer.”
1. National Institute for Health and Care Excellence. Final appraisal document. Nivolumab with ipilimumab for previously treated metastatic colorectal cancer with high microsatellite instability or mismatch repair deficiency.
Available at https://www.nice.org.uk/guidance/gid-ta10272/documents/final-appraisal-determination-document.
2. Eso Y, Shimizu T, Takeda H, et al. Microsatellite instability and immune checkpoint inhibitors: toward precision medicine against gastrointestinal and hepatobiliary cancers. J Gastroenterol. 2020;55:15–26.
3. Fujiyoshi K, Yamamoto G, et al. Metastatic Pattern of Stage IV Colorectal Cancer with High-Frequency Microsatellite Instability as a Prognostic Factor. Anticancer Res. 2017;37(1):239-247
4. Gologan A, Sepulveda AR. Microsatellite instability and DNA mismatch repair deficiency testing in hereditary and sporadic gastrointestinal cancers. Clin Lab Med. 2005;25(1):179-96.