Prognostic Nomogram and Patterns of Use of FOLFIRI-Aflibercept in Advanced Colorectal Cancer: A Real-World Data Analysis
Por:
Montes, AF, Lopez, CL, Martinez, GA, Lopez, DP, Munoz, AML, Paredes, BG, Abad, DG, Lopez, CC, Fonseca, PJ, Plazas, JG, Doldan, MCL, de Castro, EM, Canovas, MS, Puyal, MT, Ayala, BL, Martel, IJ, Flores, ML, Carmona-Bayonas, A
Publicada:
1 ago 2019
Resumen:
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.
Filiaciones:
Montes, AF:
Complexo Hosp Univ Ourense, Med Oncol Dept, Orense, Spain
Lopez, CL:
Hosp Univ Marques de Valdecilla, Med Oncol Dept, Santander, Spain
Martinez, GA:
Hosp Valle De Hebron, Med Oncol Dept, Barcelona, Spain
Lopez, DP:
Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain
Munoz, AML:
Hosp Univ Burgos, Med Oncol Dept, Burgos, Spain
Paredes, BG:
Hosp Clin San Carlos, Med Oncol Dept, Madrid, Spain
Abad, DG:
Hosp Fuenlabrada, Med Oncol Dept, Madrid, Spain
Lopez, CC:
Hosp Univ Leon, Med Oncol Dept, Leon, Spain
Fonseca, PJ:
Hosp Univ Cent Asturias, Med Oncol Dept, Oviedo, Spain
Plazas, JG:
Hosp Gen Univ Elche, Med Oncol Dept, Elche, Spain
Doldan, MCL:
Complexo Hosp Univ Ourense, Med Oncol Dept, Orense, Spain
de Castro, EM:
Hosp Univ Marques de Valdecilla, Med Oncol Dept, Santander, Spain
Canovas, MS:
Univ Murcia UMU, IMIB, Hematol & Med Oncol Dept, Hosp Univ Morales Meseguer, Murcia, Spain
Puyal, MT:
Hosp Valle De Hebron, Med Oncol Dept, Barcelona, Spain
Ayala, BL:
Hosp Univ Burgos, Med Oncol Dept, Burgos, Spain
Martel, IJ:
Hosp Fuenlabrada, Med Oncol Dept, Madrid, Spain
Flores, ML:
Hosp Univ Leon, Med Oncol Dept, Leon, Spain
Carmona-Bayonas, A:
Univ Murcia UMU, IMIB, Hematol & Med Oncol Dept, Hosp Univ Morales Meseguer, Murcia, Spain
Green Published, Bronze
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