Real-world dosing of regorafenib and outcomes among patients with metastatic colorectal cancer: a retrospective analysis using US claims data.

BACKGROUND: The randomized, dose-optimization, open-label ReDOS study in US patients with metastatic colorectal cancer (CRC) showed that, compared with a standard dosing approach, initiating regorafenib at 80 mg/day and escalating to 160 mg/day depending on tolerability increased the proportion of patients reaching their third treatment cycle and reduced the incidence of adverse events without compromising efficacy. Subsequently, the ReDOS dose-escalation strategy was included as an alternative regorafenib dosing option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. A retrospective analysis was conducted using a US claims database to assess whether inclusion of this dose-escalation strategy in NCCN Guidelines has influenced the use of flexible dosing in routine US clinical practice, and to describe clinical outcomes pre- and post-inclusion in NCCN Guidelines. METHODS: Patients with CRC in the Optum's de-identified Clinformatics® Data Mart database initiating regorafenib for the first time between January 2016 and June 2020 were stratified based on whether they initiated regorafenib pre- or post-inclusion of ReDOS in NCCN Guidelines, and in two groups: flexible dosing (< 160 mg/day; < 84 tablets in the first treatment cycle) and standard dosing (160 mg/day; ≥ 84 tablets in the first treatment cycle). The primary endpoints were the proportion of patients who initiated their third treatment cycle and the mean number of treatment cycles per group. RESULTS: 703 patients initiated regorafenib during the study period, of whom 310 (44%) initiated before and 393 (56%) initiated after inclusion of ReDOS in NCCN Guidelines. After inclusion in the guidelines, the proportion of patients who received flexible dosing increased from 21% (n = 66/310) to 45% (n = 178/393), the proportion who received standard dosing decreased from 79% (n = 244/310) to 55% (n = 215/393), the proportion who initiated their third treatment cycle increased from 36% (n = 113/310) to 46% (n = 179/393), and the mean (standard deviation) number of treatment cycles increased from 2.6 (2.9) to 3.2 (3.1). CONCLUSIONS: Following inclusion of ReDOS in NCCN Guidelines, real-world data suggest that US clinicians have markedly increased use of flexible dosing in clinical practice, potentially maximizing clinical benefits and safety outcomes for patients with metastatic CRC receiving regorafenib.

Use of FOLFOXIRI Plus Bevacizumab and Subsequent Therapies in Metastatic Colorectal Cancer: An Age-Stratified Analysis.

BACKGROUND: Treatment recommendations for metastatic colorectal cancer (mCRC) do not differ by age group; nevertheless, aggressive multiagent chemotherapy comprising FOLFOXIRI+bevacizumab (triplet+bev) is routinely administered in younger patients. This study analyzed real-world data on index triplet+bev use and subsequent systemic therapies. MATERIALS AND METHODS: This retrospective, observational cohort study was conducted in patients aged ≥ 18 years with mCRC, who were initiated on triplet+bev. Data were derived from the Optum de-identified electronic health record dataset. RESULTS: Of 36,056 patients, 14%, 36%, and 50% were aged 18-49, 50-64, and ≥ 65 years, respectively. During the study period (2010-2021), triplet+bev use increased in patients aged 18-49 years (1%-4%) but remained at approximately 3% and 1% in patients aged 50-64 and ≥ 65 years, respectively. Patient demographics and clinical characteristics varied slightly; of patients receiving triplet+bev (n = 921) versus nontriplet+bev (n = 35,132) most were male (57% vs. 52%), resided in the Midwest (54% vs. 49%) and Northeast (18% vs. 14%) US regions, and had secondary malignancies (86% vs. 73%). Following triplet+bev, most patients received subsequent therapies (including continued triplet component therapies; 97%) or subsequent "new" therapies (therapies that did not include any agents comprising triplet+bev; 57%), most frequently EGFR inhibitors (28%) and regorafenib (21%), with a similar trend among all age groups. CONCLUSIONS: Overall, this study shows that younger patients with mCRC are more likely to receive first-line triplet+bev. These results also reveal that nonchemotherapy options are often used beyond first-line triplet chemotherapy for patients with mCRC.

Self-reported and parent-reported mental health in children from low-income families in Agder, Norway: results from baseline measurements of New Patterns project participants.

BACKGROUND: Poverty may pose risks to child and adolescent mental health, but few studies have reported on this association among children and adolescents in low-income families in Norway. METHODS: Based on a sample participating in an intervention for low-income families in Norway, we report data from the survey administered at the start of the intervention. Mental health problems were measured using the Strengths and Difficulties Questionnaire (SDQ; self-report (SR) n = 148; parent/proxy-report (PR) n = 153, mean age = 10.8). Demographic and family characteristics were obtained from parent reported data. Results are presented by gender and migration background. Regression analysis was used to investigate the relative contribution of background factors to mental health symptoms. The distribution of scores is compared to UK norms. RESULTS: Participants reported relatively high scores on the Strengths and Difficulties Questionnaire (SDQ) Total Difficulties Scale (parent/proxy-report, PR mean=10.7; self-report, SR mean=10.1). Participants with non-immigrant backgrounds scored considerably higher on the Total Difficulties Scale (PR mean difference=2.9; SR 5.3) and on most other domains measured with the SDQ compared with their peers with immigration backgrounds. Participants generally scored higher than or equal to UK norms. CONCLUSION: Participants in the current study had many symptoms of mental health problems, with large differences between those with and without a migrant background. Interventions for low-income families should be based on detailed knowledge about differences in family risks, resources and needs.

Eficácia e Segurança de Regorafenibe em Pacientes com Características de Bom Prognóstico no Tratamento do Câncer Colorretal Metastático: Análise de Subgrupo do Estudo CORRECT / Efficacy and Safety of Regorafenib in Patients with Characteristics of Good Prognosis in the Treatment of Metastatic Colorectal Cancer: Subgroup Analysis of CORRECT Study / Eficacia y Seguridad de Regorafenib en Pacientes con Características de Buen Pronóstico en Tratamiento del Cáncer Colorrectal Metastásico: Análisis de Subgrupo del Estudio CORRECT

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

Introduction: Colorectal cancer (CRC) is the second most common and when metastatic, it has a five-year survival rate of 14%. Regorafenib is an approved TKI for metastatic colorectal cancer (mCRC) with a proven increase in overall survival (OS). Objective: To investigate the efficacy and safety results of regorafenib in patients with mCRC and good prognostic characteristics (GPC). Method: Subgroup analysis of the CORRECT study, with participants divided according to GPC, following the criteria: Eastern Cooperative Oncology Group (ECOG) 0, duration of metastatic disease greater than 18 months, up to three metastatic sites and absence of liver metastasis. Efficacy compared with stratified log-rank test and hazard ratios (HR) calculated with the Cox model. Results: Of the 760 participants randomized, 292 (34.5%) had GPC; 185 (63.4%) received regorafenib; and 107 (35.6%) received placebo. For the GPC group, the median OS was 10.9 months (95%CI:8.8-12.3) for regorafenib and 7.3 months (95%CI:5.6-9.1) for placebo, with 39% of reduction of the risk of death (HR 0.61; 95% CI:0.43-0.88; p=0.0069). The median progression-free survival (PFS) was 3.5 months (95%CI:3.0-3.9) versus 1.8 months (95%CI:1.7-1.8) respectively, with 61% of reduced risk of disease progression or death (HR 0.39; 95%CI:0.30-0.52; p<0.0001). Grade 3 and 4 adverse events were more frequent for regorafenib. After setting baseline for quality of life scores (EQ-5D), these declined less for regorafenib compared to placebo (0.687 versus 0.592) with a significant difference of 0.09. Conclusion:GPC patients who received regorafenib improved OS and PFS with less deterioration of quality-of-life compared to placebo

Introducción: El cáncer colorrectal (CCR) es el segundo más frecuente y cuando presenta metástasis tiene una supervivencia a los cinco años del 14%. Regorafenib es un inhibidor de la tirosina quinasa (ITQ) aprobado para CCR metastásico (CCRm) con un aumento comprobado en la supervivencia general (SG). Objetivo: Explorar los resultados de eficacia y seguridad de regorafenib en pacientes con CCRm y características de buen pronóstico (CBP). Método: Análisis de subgrupos del estudio CORRECT, con participantes divididos según CBP, siguiendo los criterios: Eastern Cooperative Oncology Group (ECOG) 0, duración de la enfermedad metastásica mayor a 18 meses, hasta tres sitios metastásicos y ausencia de metástasis hepática. Eficacia comparada con la prueba de log-rank estratificada y hazad ratios (HR) calculados con el modelo de Cox.Resultados: De los 760 participantes aleatorios, 292 (34,5%) tenían CBP; 185 (63,4%) recibieron regorafenib; 107 (35,6%) recibieron placebo. Para el grupo de CBP, la mediana de SG fue de 10,9 meses (IC95%:8,8-12,3) para regorafenib y de 7,3 meses (IC95%:5,6-9,1) para placebo, con una reducción del riesgo de muerte del 39% (HR 0,61; IC95%:0,43-0,88; p=0,0069). La mediana de supervivencia libre de progresión (PFS) fue de 3,5 meses (IC95%:3,0-3,9) frente a 1,8 meses (IC95%:1,7-1,8) respectivamente, con un 61% de riesgo reducido de progresión de la enfermedad o muerte (HR 0,39; IC95%:0,30-0,52; p<0,0001). Los eventos adversos de grado 3 y 4 fueron más frecuentes con regorafenib. Después de establecer la línea de base para las puntuaciones de calidad de vida (EQ-5D), estas disminuyeron menos con regorafenib en comparación con placebo (0,687 frente a 0,592) con una diferencia significativa de 0,09. Conclusión: Los pacientes con CBP que recibieron regorafenib mejoraron la SG y la SLP con un menor deterioro en la calidad de vida en comparación con el placebo