Targeting Angiogenesis and Tumor Microenvironment in Metastatic Colorectal Cancer: Role of Aflibercept

Table 2

Aflibercept in mCRC has been clinically developed in several phases I-II clinical trials and in a final phase III randomized trial. This table briefly summarizes results of efficacy, activity, and safety in published/presented clinical trials with aflibercept in mCRC.

Study	Phase	Setting	Patients (num.)	Aflibercept schedule	Efficacy	Safety (grade 3/4 toxicities)
Yoshino et al. [92]; Invest New Drugs 2013 Aug; 31 (4): 910–7	I	mCRC	16	2–4 mg/kg + FOLFIRI	ORR (𝑛=13 at 4 mg/kg ): 7.7%; SD: 69.2%; Median PFS: 7.6 mo	Neutropenia: 75%; Hypertension: 25%
Verslype et al. [96]; ASCO 2008 Abstract (14540)	I	Recurrent solid tumors; (70% CRC)	27	4 mg/kg or; PBO + FOLFIRI; Cy 1 → 4 mg/kg + FOLFIRI q2 wk	ORR: 15.4%; SD: 65.4%	Neutropenia: 37.0%; Fatigue: 29.6%; Hypertension: 29.6%; Dyspnea: 22.2%
van Cutsem et al. [91]; Eur J Cancer. 2013; 49: 17–24	I	Recurrent solid tumors; (61% CRC)	38	2, 4, 5, and 6 mg/kg,; and FOLFIRI	Not a study end point	Serious AEs in 27 patients; 50%, 67%, 70%, and 58% of patients; at aflibercept 2, 4, 5, and 6 mg/kg, respectively
Tang et al. [93]; J Clin Oncol 2008; 26 (suppl): abstract 4027	II	Previously treated mCRC	51	4 mg/kg q2wk; monotherapy	DCR 30% vs 29%; PFS 3.4 vs 2.0 months; (bev. pretreated vs naïve)	Hypertension, proteinuria 8%; fatigue, headache 6%
Tang et al. [94]; Clin Cancer Res 2012; 18: 6023–31	II	Recurrent; CRC	75	4 mg/kg q2wk; monotherapy	PFS 2.4 vs 2.0 months; (bev. pretreated vs naïve)	Hypertension 9.1%; Proteinuria 9%; Fatigue, headache 5%
AFFIRM; Pericay et al. [95]; Ann Oncol 2012; 23 (Suppl. 4) Abstract 0024	II Ran	Untreated mCRC	235	4 mg/kg ± mFOLFOX6; q2wk	12 months PFS rate: 25.8% vs 21.2%; (aflibercept + mFOLFOX6 vs mFOLFOX6)	Grade 3/4 toxicities > 5% higher in aflibercept arm; Hypertension, neutropenia, diarrhea; Infection
Van Cutsem et al. [97]; J Clin Oncol 2012; 30: 3499–506	III Ran	Oxaliplatin pretreated mCRC	1226	4 mg/kg ± FOLFIRI q2wk	OS = 13.50 vs 12.06 months; PFS: 6.90 vs 4.67 months; ORR: 19.8% vs 11.1%; (aflibercept + FOLFIRI vs FOLFIRI)	Diarrhea 19.3%; Neutropenia 36.7%; Stomatitis and ulceration 13.7%; Hypertension 19.3%; Proteinuria 7.9%; TVE 7.9%

bev.: bevacizumab; DCR: disease control rate; mCRC: metastatic colorectal cancer; mFOLFOX6: modified FOLFOX6; num.: number; ORR: objective response rate; OS: overall survival; PBO: placebo; PFS: progression-free survival; q2wk: every 2 weeks; Ran: randomized; SAEs: severe adverse events; SD: stable disease; TVE: thromboembolic venous events; vs: versus.