Gastroenterology Research and Practice / 2014 / Article / Tab 2

Review Article

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.

StudyPhaseSettingPatients (num.)Aflibercept scheduleEfficacySafety (grade 3/4 toxicities)

Yoshino et al. [92]  
Invest New Drugs 2013 Aug; 31 (4): 910–7
ImCRC162–4 mg/kg + FOLFIRIORR ( 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)
IRecurrent solid tumors
(70% CRC)
274 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
IRecurrent solid tumors
(61% CRC)
382, 4, 5, and 6 mg/kg,
and FOLFIRI
Not a study end pointSerious 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
IIPreviously treated mCRC 514 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
IIRecurrent
CRC
754 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 RanUntreated mCRC235 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 RanOxaliplatin pretreated mCRC12264 mg/kg ± FOLFIRI q2wkOS = 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.