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Clinical management

Treatment options

3.2

The aim of treatment for mCRC is to prolong survival and improve quality of life. The treatment options for mCRC include:

The initial treatment choice depends on the presence or absence of 3 molecular markers: BRAF 600, RAS wild-type, and microsatellite instability/mismatch repair deficiency. When these molecular markers are present, specific biologicals and chemotherapy are usually offered as first- and second-line treatments. In the absence of these molecular markers, the committee understood that treatment for mCRC consists of various combinations or sequences of chemotherapy agents including FOLFOX (folinic acid plus fluorouracil plus oxaliplatin), CAPOX (capecitabine plus oxaliplatin) and FOLFIRI (folinic acid plus fluorouracil plus irinotecan). For this evaluation, the company positioned trifluridine–tipiracil plus bevacizumab for use at third line or later, in line with the marketing authorisation (see section 2.1). The EAG agreed with this positioning. But, it highlighted that defining third-line treatment is difficult and depends on the use in combination of previous chemotherapy agents. The clinical experts also highlighted that combinations of chemotherapy may be used in a course of treatment, which increases the difficulty in defining lines of treatment in mCRC. For example, there is increased use of FOLFOXIRI, which uses both oxaliplatin and irinotecan. They thought that a better definition for implementing the marketing authorisation would be after both oxaliplatin and irinotecan had been trialled. The committee concluded that this positioning as a treatment at third line or later was clinically appropriate. But, it noted the potential for concerns about the generalisability of the trial evidence to clinical practice in the NHS because of differences in treatment combinations given earlier in the pathway.

Comparators

3.3

The company's proposed comparators were narrower than the treatment options listed in the NICE final scope. The company proposed trifluridine–tipiracil alone, regorafenib and best supportive care as comparators. This was because they reflect clinical practice and are in line with NICE's technology appraisal guidance on regorafenib for previously treated mCRC. The Cancer Drugs Fund lead explained that trifluridine–tipiracil alone has a better toxicity profile than regorafenib. They added that, although people may have sequential treatment with regorafenib and trifluridine–tipiracil alone in either order, most will have trifluridine–tipiracil alone first. The patient experts highlighted that choice for people with mCRC is an important consideration. They added that the choice of regorafenib or trifluridine–tipiracil alone may be affected by the person's current performance status and toxicity profile of the treatment. The clinical experts explained that, for some people with mCRC, regorafenib would be a more suitable choice of treatment at third line than trifluridine–tipiracil alone. But, the clinical experts also explained that people eligible for best supportive care would generally not be well enough to have active treatment (including trifluridine–tipiracil plus bevacizumab). The committee concluded that, in clinical practice, the choice between trifluridine–tipiracil alone and regorafenib depends on the person with mCRC's choice and clinical judgement, so both are valid comparators. The committee noted that this treatment would not be used in any person that was not able to have trifluridine–tipiracil alone or regorafenib. So, it thought that the comparison with best supportive care was less relevant in terms of which treatment it would likely displace at this position in the treatment pathway.