Observed benefit and safety of aflibercept in elderly patients with metastatic colorectal cancer: An age-based analysis from the randomized placebo-controlled phase III VELOUR trial

Ruff, Paul; Cutsem, Éric Van; Lakomý, Radek; Prausová, Jana; Hazel, Guy A. Van; Moiseyenko, Vladimir; Soussan-Lazard, Karen; Dochy, Emmanuelle; Magherini, E.; Macarulla, Teresa; Papamichael, Demetris

doi:10.1016/j.jgo.2017.07.010

Cited by 32 publications

(24 citation statements)

References 25 publications

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“…Although the tolerance profile appears to be slightly better here than in the pivotal trial, it must be taken into account that serious toxicity‐related hospitalizations were still greater among elderly patients (≥65 years). This result essentially coincides with those of Ruff et al who found an increase in the toxicity profile of individuals aged more than 65 years in an age‐based analysis of the VELOUR trial . This group continues to be more complex in second‐line treatment for mCRC .…”

Section: Discussionsupporting

confidence: 88%

“…In and of itself, this is certainly a valid research objective that should interest the clinician. This series confirms that, indeed, elderly patients are a commonly seen group who are prone to more serious AEs, as previously reported by other authors , which appears to justify clinicians’ use of modified regimens to reduce toxicities when confronted with this situation . Therefore, in addition to helping us describe the usual management patterns in these individuals with this treatment alternative and in this specific clinical context, this analysis of routine clinical practice has enabled us to develop a nomogram with the potential to optimize treatment outcomes, as well as being applicable in developing subsequent clinical trials.…”

Section: Discussionsupporting

confidence: 85%

“…Although the benefit was maintained across all strata , a post hoc analysis indicated that a profile of good and poor responders could be clinically defined (e.g., based on the Eastern Cooperative Oncology Group performance status [ECOG PS], time to relapse after adjuvant treatment, and number of metastases) . Furthermore, another subanalysis confirmed that, despite efficacy data (PFS and OS) being consistent across age groups, grade 3–4 adverse events (AEs) were more common in the elderly . Likewise, a registry of real‐world data suggested that clinical course during treatment with aflibercept (risk of progression or death) was heterogeneous and possibly affected by simple clinical variables .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…In a post hoc analysis, the incidence of grade 3/4 AEs was higher for patients ≥ 65 years of age than for those < 65 years of age in both the aflibercept (89.3% vs 80.5%) and placebo (67.4% vs 59.4%) arms. Interaction tests for grade 3/4 antiangiogenic agent-related AEs suggested no heterogeneity between the older and younger patient populations (p > 0.1) [12]. Similarly, another post hoc analysis did not identify any differences in all grade and grade 3/4 AEs between the subgroup of patients with better and poorer efficacy [13].…”

Section: Global Studiesmentioning

confidence: 90%

Safety of Aflibercept in Metastatic Colorectal Cancer: A Literature Review and Expert Perspective on Clinical and Real-World Data

Muro

Salinardi

Singh

et al. 2020

Cancers

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Background: Metastatic colorectal cancer (mCRC) represents a substantial health burden globally and an increasing challenge in Asian countries. Treatment options include chemotherapy plus a vascular endothelial growth factor (VEGF) inhibitor (such as bevacizumab, aflibercept or ramucirumab), or anti-epidermal growth factor receptor (EGFR) therapies. Aflibercept, a recombinant fusion protein, has been approved for treatment of mCRC in combination with FOLFIRI for patients whose disease progresses during or after treatment with an oxaliplatin-containing regimen, based on its efficacy and tolerability profile in clinical trials. This report aims to provide an overview of both clinical and real-world evidence and experience on the use of aflibercept in routine clinical practice, with a focus on European, American and Asian populations. Methods: A literature search was conducted in PubMed (on 28th February 2019) using the search terms ("aflibercept") and ("Colorectal"OR"CRC") to identify publications containing information on aflibercept-containing regimens. Results: The adverse events (AE) profile was similar between geographical locations. Across trials, real-world and retrospective studies, grade ≥ 3 hypertension and proteinuria were amongst the most frequently reported AEs. Conclusions: The safety profile of aflibercept is generally manageable and comparable across various geographic locations.

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“…Афлиберцепт, как и бевацизумаб, неэффективен при монотерапии пациентов с метастатическим КРР [8]. При этом в клинических исследованиях III фазы было показано, что афлиберцепт улучшает ВБП, ОВ и частоту ответа на лечение при использовании в сочетании с режимом FOLFIRI во 2-й линии терапии метастатического КРР [50][51][52].…”

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New therapeutic agents for metastatic colorectal cancer: literature review

Забелин

Гордеев

Кочкина

et al. 2018

Onkol. koloproktol.

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Observed benefit and safety of aflibercept in elderly patients with metastatic colorectal cancer: An age-based analysis from the randomized placebo-controlled phase III VELOUR trial

Cited by 32 publications

References 25 publications

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

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

Safety of Aflibercept in Metastatic Colorectal Cancer: A Literature Review and Expert Perspective on Clinical and Real-World Data

New therapeutic agents for metastatic colorectal cancer: literature review

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