Title: Regorafenib for treating metastatic colorectal cancer [ID4002] (Review of TA334)
Funder: Department of Health and Social Care

Abstract: Colorectal cancer is a malignant tumour arising from the lining of the large intestine (colon and rectum). Metastatic colorectal cancer refers to disease that has spread beyond the large intestine and nearby lymph nodes. This type of cancer often first spreads to the liver, but metastases may also occur in other parts of the body, including the lungs, brain and bones. Most colorectal cancers are adenocarcinomas, these start in glands that line the insides of the colon and rectum. _x000D_ _x000D_ There were 33,815 cases of colon cancer and 16,628 cases of rectum cancer in the UK in 2020, accounting for 11% of all cancers in the UK.[1] Five-year prevalence of colon cancer is 149.34 per 100,000, and 5-year prevalence of rectum cancer is 80.16 per 100,000.[1] 58% of new cases of colorectal cancer in the UK were in people aged over 65 years, but it can also affect young people too. [2] _x000D_ _x000D_ The cause of colorectal cancer is uncertain, however studies have shown the frequency of colorectal cancer is higher in countries where people eat a diet high in fat and low in fibre.[3],[4] Two inherited disease can also increase the risk of developing colorectal cancer: familial adenomatous polyposis and hereditary non-polyposis colon cancer. [4] A history of severe ulcerative colitis or Chron’s disease affecting the large bowel may increase the risk of developing colorectal cancer. [4] _x000D_ _x000D_ Metastatic colorectal cancer treatment aims to prolong survival and improve quality of life. Metastatic colorectal cancer treatment can involve a combination of surgery (to resect the primary tumour or the metastases), chemotherapy (to make the tumour or metastases resectable, or to manage the cancer), biological therapy, and radiotherapy. For people with untreated metastatic colorectal cancer, NICE technology appraisal 61 recommends intravenous fluorouracil/folinic acid (5-FU/FA) or capecitabine. NICE guideline 151 also recommends either folinic acid plus fluorouracil plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX) for untreated disease. _x000D_ _x000D_ For people with previously treated metastatic colorectal cancer NICE guideline 151 recommends folinic acid plus fluorouracil plus irinotecan (FOLFIRI), after either FOLFOX or CAPOX. Established clinical management for previously treated metastatic colorectal cancer is considered to be single-agent irinotecan (after FOLFOX) or raltitrexed (for patients with advanced colorectal cancer who are intolerant to 5-FU/FA, or for whom these drugs are not suitable). NICE technology appraisal 405 recommends trifluridine–tipiracil, if fluoropyrimidine-, oxaliplatin- or irinotecan-based chemotherapies, anti-vascular endothelial growth factor (VEGF) agents and anti-EGFR agents have failed or when these therapies are not suitable. If standard therapies are unsuccessful, not tolerated or contraindicated, people are treated with best supportive care to manage the symptoms and complications of the condition. _x000D_ _x000D_ Nivolumab with ipilimumab can be offered as a treatment for those with high microsatellite instability or mismatch repair deficiency after fluoropyrimidine-based combination chemotherapy (NICE TA716). For those with BRAF V600E mutationpositive metastatic colorectal cancer who have had previous systemic treatment encorafenib plus cetuximab is a treatment option (NICE TA668)._x000D_ _x000D_ References_x000D_ 1. United Kingdom Fact sheet, International Agency for Research on Cancer. Accessed February 2022._x000D_ 2. Office for National Statistics, Cancer registration statistics, England. Accessed February 2022._x000D_ 3. Cancer Research UK, Bowel cancer statistics. Accessed February 2022._x000D_ 4. The Royal Marsden NHS Foundation Trust, Colorectal cancer. Accessed February 2022.

Lay abstract: To appraise the clinical and cost effectiveness of regorafenib within its marketing authorisation for treating metastatic colorectal cancer.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS