Background: Regorafenib (R) and Trifluridine/Tipiracil ± bevacizumab (T) are approved for treating refractory metastatic colorectal cancer (mCRC) but their optimal sequence is unclear. This study describes the characteristics/clinical outcomes of patients with mCRC in U.S. clinical practice treated sequentially with R-T or T-R. Methods: A retrospective cohort study of 818 patients treated with R-T or T-R between January 2015 and November 2022 was conducted using an electronic health record-derived database. The primary objective was to describe the demographic/clinical characteristics and biomarker status of patients treated with R-T or T-R, stratified by treatment line/age. Secondary objectives were to evaluate/estimate the frequency of neutropenia and myelosuppression-related treatments, the number/type of subsequent therapies, time to treatment discontinuation (TTD), and overall survival (OS). Results: Baseline characteristics were similar among patients who received R-T (n = 393) or T-R (n = 425). Lower rates of moderate/severe neutropenia (26%/12% vs. 32%/16%) and granulocyte colony-stimulating factor/erythropoietin use (22% vs. 24%) were observed with R-T versus T-R. The median TTD was 8.7 months and 8.5 months with R-T versus 8.1 months and 7.9 months with T-R as third- and fourth-line treatment, respectively. The median OS was 13.1 months and 11.6 months with R-T versus 11.5 months and 10.3 months with T-R as third- and fourth-line treatment, respectively. Conclusions: This study did not show a statistically significant difference in OS with R-T versus T-R. Although limited by its retrospective nature, the study suggested R-T may be preferable to T-R given the observed reduction in neutropenia/myelosuppression-related treatments.

Background: Several narrative reports document long-term responses to regorafenib treatment in patients with metastatic colorectal cancer (mCRC). However, no large-scale study has assessed long-term responses and there are no established predictors of potential long-term benefit. We carried out an observational study of characteristics of patients treated in real-world clinical practice in the USA using duration of treatment (DoT) as a surrogate for treatment response. Patients and Methods: This retrospective cohort study used a de-identified electronic health record-derived database and included patients aged ≥18 years with mCRC who initiated regorafenib monotherapy between 1 July 2013 and 30 June 2023. Patient cohorts were defined by DoT ≥4 months (LTR4), ≥5 months (LTR5), or ≥6 months (LTR6) and are not mutually exclusive. Results: Of 2444 patients who initiated regorafenib monotherapy during the study, those with long-term response were analyzed: 544 had LTR4 (22%), 367 had LTR5 (15%), and 250 had LTR6 (10%). Most patients with long-term responses had left-sided tumors (65–70%), Eastern Cooperative Oncology Group performance status of 0/1 (67–68%), and liver metastases (55–61%) and had received prior bevacizumab treatment (60–67%). The median age in each group was 66 years, and patients most frequently initiated regorafenib as third-line treatment (31–33%). Median time to regorafenib discontinuation was 6.0–9.3 months among long-term responders. Conclusions: Most patients with long-term responses to regorafenib had favorable performance status at treatment initiation, left-sided tumors, and liver metastases and had received prior bevacizumab treatment. The study highlights that patients in the real-world setting were able to tolerate and maintain long-term responses to regorafenib treatment.

Introdução: O câncer colorretal (CCR) é o segundo mais incidente e, quando metastático, apresenta taxa de sobrevida de 14% em cinco anos. Regorafenibe é um inibidor de tirosina-quinase (ITQ) aprovado para CCR metastático (CCRm) com aumento comprovado de sobrevida global (SG). Objetivo: Explorar resultados de eficácia e segurança de regorafenibe em pacientes com CCRm e características de bom prognóstico (CBP). Método: Análise de subgrupo do estudo CORRECT, com participantes divididos de acordo com CBP, seguindo os critérios: Eastern Cooperative Oncology Group (ECOG) 0, tempo de doença metastática maior que 18 meses, até três sítios metastáticos e ausência de metástase hepática. Eficácia comparada com teste de log-rank estratificado e hazad ratios (HR) calculados com o modelo de Cox. Resultados: Dos 760 participantes randomizados, 292 (34,5%) apresentavam CBP; 185 (63,4%) receberam regorafenibe; 107 (35,6%), placebo. Para o grupo CBP, a mediana SG foi 10,9 meses (IC95%:8,8-12,3) para regorafenibe e 7,3 meses (IC95%:5,6-9,1) para placebo, com 39% de redução no risco de morte (HR 0,61; IC95%:0,43-0,88; p=0,0069). A mediana de sobrevida livre de progressão (SLP) foi de 3,5 meses (IC95%:3,0-3,9) versus 1,8 mês (IC95%:1,7-1,8) respectivamente, com 61% de redução no risco de progressão da doença ou morte (HR 0,39; IC95%:0,30-0,52; p<0,0001). Os eventos adversos graus 3 e 4 foram mais frequentes para regorafenibe. Após definição de valor basal para escores de qualidade de vida (EQ-5D), estes decaíram menos para regorafenibe comparados com placebo (0,687 versus 0,592) com diferença significativa de 0,09. Conclusão: Pacientes com CBP que receberam regorafenibe melhoraram SG e SLP com menor deterioração da qualidade de vida comparado com placebo.