Prognostic Nomogram and Patterns of Use of FOLFIRI-Aflibercept in Advanced Colorectal Cancer: A Real-World Data Analysis

The oncologist

article

Ana Fernández Montes¹  Javier Gallego Plazas²  María Carmen López Doldán¹  Eva Martínez de Castro³  Manuel Sánchez Cánovas⁴  María Tobeña Puyal⁵  Beatriz Llorente Ayala⁶  Ignacio Juez Martel⁷  Mariana López Flores⁸  Alberto Carmona-Bayonas⁴  Carlos López López³  Guillem Argilés Martínez⁵  David Páez López⁹  Ana María López Muñoz⁶  Beatriz García Paredes^1,10  David Gutiérrez Abad⁷  Carmen Castañón López⁸  Paula Jiménez Fonseca^1,11 

[1] Medical Oncology Department, Complexo Hospitalario Universitario de Ourense;Medical Oncology Department, Hospital General Universitario de Elche;Medical Oncology Department, Hospital Universitario Marqués de Valdecilla;Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, Universidad de Murcia (UMU), Instituto Murciano de Investigación Biosanitaria (IMIB);Medical Oncology Department, Hospital Vall d'Hebrón;Medical Oncology Department, Hospital Universitario de Burgos;Medical Oncology Department, Hospital de Fuenlabrada;Medical Oncology Department, Hospital Universitario de León;Medical Oncology Department, Hospital de la Santa Creu i Sant Pau;Medical Oncology Department, Hospital Clínico San Carlos;Medical Oncology Department, Hospital Universitario Central de Asturias

关键词: Aflibercept;    Colorectal cancer;    Antiangiogenic;    Real-world data;    Nomogram;    Prognosis;    Survival;   

DOI  :  10.1634/theoncologist.2018-0824

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Introduction The VELOUR study evaluated the efficacy and safety of adding aflibercept to FOLFIRI (fluorouracil, leucovorin, irinotecan) in second-line therapy for metastatic colorectal cancer (mCRC). However, a nomogram that can stratify patients according to prognosis is unavailable, and the frequency and effect of the pragmatic use of modified schedules in actual practice remains unknown. Method The sample consists of 250 patients with mCRC treated with aflibercept and irinotecan-based chemotherapy at nine Spanish academic centers between January 2013 and September 2015. The result of a Cox proportional hazards model regression for overall survival (OS), adjusted for covariates available in daily practice, was represented as a nomogram and web-based calculator. Harrell's c-index was used to assess discrimination. Results The prognostic nomogram for OS includes six variables: Eastern Cooperative Oncology Group performance status, tumor location, number of metastatic sites, mutational status, better response to previous treatment(s), and carcinoembryonic antigen. The model is well calibrated and has acceptable discriminatory capacity (optimism-corrected c-index, 0.723; 95% confidence interval [CI], 0.666–0.778). Median OS was 6.1 months (95% CI, 5.1–8.8), 12.4 months (95% CI, 9.36–14.8), and 22.9 months (95% CI, 16.6–not reached) for high-, intermediate-, and low-risk groups, respectively. Age, comorbidity, or use of modified FOLFIRI regimens did not affect prognosis in this series. Grade 3–4 adverse events were less common following modified schedules. The admission rate because of toxicity was higher in ≥65 years (9.7% vs. 19.6%; odds ratio, 2.26; p = .029). Conclusion We have developed and internally validated a prognostic model for use in individuals with colorectal cancer initiating therapy with FOLFIRI-aflibercept to predict both OS and the effect of pragmatic modifications of the classic regime on efficacy and safety. This can aid in decision making and in designing future trials. Implications for Practice In this study, the authors developed and conducted the internal validation of a prognostic nomogram that makes it possible to stratify patients who are eligible for second-line FOLFIRI-aflibercept based on their probability of survival. This model was developed in a multicenter sample from nine Spanish hospitals. Furthermore, to increase the study's validity, the practical use of aflibercept in this setting was investigated, including doses or pragmatic modifications. The results suggest that the modified schedules often used in this daily clinical practice-based patient population are associated with less severe toxicity without apparent detriment to survival endpoints. It is believed that these data complement the information provided by the VELOUR trial and are relevant for the oncologist in treating colon cancer in the second-line setting.

【 授权许可】

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