Efficacy of aflibercept with FOLFOX and maintenance with fluoropyrimidine as first‑line therapy for metastatic colorectal cancer: GERCOR VELVET phase�II study

Abstract

Aflibercept in combination with 5-fluorouracil (5-FU)/irinotecan improves overall survival in the second-line therapy of patients with metastatic colorectal cancer (mCRC). In this study, we evaluated the effects of aflibercept in first-line therapy with FOLFOX followed by maintenance with fluoropyrimidine. VELVET was a prospective, single-arm multicenter phase II study (completed). Patients with previously untreated, unresectable, evaluable or measurable mCRC, with an age ≥18 years, and an ECOG performance status of 0-2 received 6 cycles of modified FOLFOX7 (5-FU/folinic acid and oxaliplatin) with aflibercept at 4 mg/kg every 2 weeks followed by maintenance therapy with fluoropyrimidine with aflibercept until disease progression or limiting toxicity. The reintroduction of oxaliplatin was performed at first progression. The primary endpoint was progression-free survival (PFS) at 6 months. From May, 2013 to May, 2014, 49 patients were included and 48 were evaluable for response. In total, 33 patients (67.4%) were alive without progression at 6 months. The Kaplan-Meier survival 6-month and 1-year PFS rates were 79.1 and 36.1%, respectively, and the median PFS was 9.3 months (95% CI, 8.3-12.5). The objective response rate was 59.2% (N=29/49). The most common (≥10%) grade 3-4 adverse events were hypertension (23%), fatigue (15%), neutropenia (12%), neuropathy (12%) and stomatitis (10%). Three (6%) treatment-related deaths occurred: One from stroke, one from pulmonary embolism and one from neutropenic sepsis. On the whole, this study demonstrates the efficacy of aflibercept in combination with an oxaliplatin-based regimen in the first-line therapy of patients with mCRC. A strict monitoring of blood pressure and immediate management of hypertension during therapy is mandatory.

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

“…Guidance for the management of clinically relevant AEs is available [48]. Of note, strict monitoring of blood pressure and immediate management of hypertension during therapy is mandatory [19]. In the large randomized trial of aflibercept plus FOLFIRI versus placebo plus FOLFIRI, although grade 3/4 AEs were more frequent in the aflibercept arm, they occurred in early treatment cycles and decreased sharply following initial presentation [14].…”

“…The most frequently occurring grade 3/4 AEs were hypertension (23%), fatigue (15%), neutropenia (laboratory measurement: 12%), neuropathy (12%) and stomatitis (10%). There were three (6%) treatment-related deaths due to stroke, pulmonary embolism and neutropenic sepsis [19]. In a study by the Hellenic Cooperative Oncology Group, first-line aflibercept plus FOLFIRI was evaluated in 73 patients with mCRC ( Figure 3).…”

Relevance of Pharmacogenomics and Multidisciplinary Management in a Young-Elderly Patient With KRAS Mutant Colorectal Cancer Treated With First-Line Aflibercept-Containing Chemotherapy

“…Adjuvant fast relapsers showed poorer efficacy and no survival benefit from addition of aflibercept (10.4 vs. 9.6 months) (7,8); in Spanish reallife experience, PFS was 5.3-6.8 months (29,30) (31,32). Aflibercept addition to mFOLFOX for six cycles, followed by maintenance and oxaliplatin reintroduction at progression, gained PFS 9.3 months (33). Aflibercept/FOLFIRI reached ORR 61.3% and PFS 8.4 months (34).…”

“…Aflibercept vs. bevacizumab added to mFOLFOX6 reported equivalent median PFS 8.48 months and ORR 49.1 vs. 45.9%; RAS / BRAF mutations did not significantly correlate with PFS ( 31 , 32 ). Aflibercept addition to mFOLFOX for six cycles, followed by maintenance and oxaliplatin reintroduction at progression, gained PFS 9.3 months ( 33 ). Aflibercept/FOLFIRI reached ORR 61.3% and PFS 8.4 months ( 34 ).…”

Deeskalacja terapii systemowej zaawansowanego raka jelita grubego – uzasadniona praktyka kliniczna w aspekcie skuteczności i bezpieczeństwa

“…The data concerning maintenance therapy with aflibercept is very limited. In one arm, second phase VELVET prospective study [24], the patients, previously untreated for mCRC received FOLFOX with aflibercept (1-6 cycles), and then maintenance therapy with fluoropyrimidine with aflibercept (4 mg/kg every 2 weeks) until the disease progression or the occurrence of toxicity. At the moment of progression, therapy with oxaliplatin was resumed.…”