Maximising clinical benefit with adequate patient management beyond the second line in mCRC

Abstract

New therapeutic options for refractory metastatic colorectal cancer (mCRC) include trifluridine/tipiracil (TAS-102) and regorafenib. However, the optimal chemotherapeutic regimen for use of each agent beyond the second line for patients with mCRC remains unclear and various factors may influence treatment decision. Available efficacy data suggest treatment with either trifluridine/tipiracil or regorafenib may be appropriate as both can extend patient survival. Thus, the safety profiles of each agent, along with patient performance status, are likely to determine treatment choice. The safety profiles of trifluridine/tipiracil and regorafenib are markedly different: higher levels of non-haematological adverse events such as fatigue, diarrhoea, hypertension and hand-foot skin reaction are reported with regorafenib, while haematological events such as neutropaenia are more common with trifluridine/tipiracil. In general, neutropaenia is a manageable treatment-related toxicity, while hand-foot skin reaction can be troublesome for patients, affecting their ability to carry out everyday activities and get on with their lives, while also affecting treatment adherence. Thus, the occurrence of any potential adverse effects and patient adherence should be closely monitored at each clinic visit. As quality of life is an important issue for patients with mCRC, it is important to balance extended survival and the likely quality of this extended life. Likewise, discussing possible side effects along with treatment expectations with patients can greatly facilitate adherence to therapy, and ultimately improve patients’ quality of life and eventual clinical outcomes.

Retrospective Study of Regorafenib Versus TAS-102 Efficacy and Safety in Chemorefractory Metastatic Colorectal Cancer (mCRC) Patients: A Multi-institution Real Life Clinical Data

“…Because of worsen regorafenib-related events, it is possible that regorafenib-related AEs affected disease progression during treatment and prompted treatment discontinuation. Therefore, it is highly important to consider toxicity-driven dosing in order to determine treatment choice 15 .…”

Systematic review and network meta-analyses of third-line treatments for metastatic colorectal cancer

“…From a clinical perspective, the adverse event profiles of each agent, along with patient performance status, are likely to determine treatment choice (Argiles et al 2019 ). While ECOG performance statuses 1–2 are considered negative prognostic factors for each intervention, the adverse event profile of SIRT using Y-90 resin microspheres is superior to both regorafenib and TAS-102, with a low incidence of all-grade or grade 3–4 AEs known to severely affect patient quality of life, such as diarrhea, hand–foot skin reaction, vomiting, or fatigue.…”

“…Effective physician–patient communication is an essential element in ensuring appropriate treatment selection, and for setting expectations for treatment outcomes and adverse event incidence. As both regorafenib and TAS-102 are orally administered, patient adherence to the choice of treatment is also essential (Argiles et al 2019 ). From the patient perspective, SIRT using Y-90 resin microspheres represents a relevant alternative with lower administration burden for the patient and no degradation of quality of life (Cosimelli et al 2010 ).…”

How we treat metastatic colorectal cancer

“…In the absence of head-to-head comparative trials, choice of the sequence between the two drugs should be made according to patient’s characteristics and comorbidity, considering the different toxicity profile. 30 In fact, trifluridine/tipiracil seems more manageable but with higher prevalence of neutropaenia. For regorafenib, dose is an issue and an escalating dose could permit a greater efficacy without affecting QoL, as described in several recent trials.…”