Dual VEGF/VEGFR inhibition in advanced solid malignancies

Figures & data

Table 1. Toxicity data: Grade ≥3 toxicities and toxicities of special interest

Grade	≥3	All grade	≥3	All grade
Toxicity	n	n	%	%
Fatigue	3	17	13.64	77.27
Hypertension	9	16	40.91	72.73
Thrombocytopenia	5	15	22.73	68.18
Nausea	1	13	4.55	59.09
Oral mucositis	2	12	9.09	54.55
Anemia	1	8	4.55	36.36
Lymphopenia	1	8	4.55	36.36
Diarrhea	1	7	4.55	31.82
Neutropenia	2	6	9.09	27.27
Palmar–plantar erythrodysesthesia syndrome	1	5	4.55	22.73
ALT elevation	1	4	4.55	18.18
Thrombotic microangiopathy	1	4	4.55	18.18
Pain	1	4	4.55	18.18
Hypophosphatemia	1	4	4.55	18.18
Haptoglobin reduction	0	4	0.00	18.18
Vomiting	1	3	4.55	13.64
Abdominal pain	1	2	4.55	9.09

Figure 1. Waterfall plot of best responses. Patients with new lesions were empirically assigned a 20% increase in target tumor measurement for accurate reflection of best response.

Table 2. Markers of angiogenesis in patients treated with dual VEGF/VEGFR inhibition

	Median level baseline (n = 13)^a	Median level week 4 (n = 13)^a	Median level week 6 (n = 9)^a	P value^b baseline vs week 4	P value^b baseline vs week 6	P value^b week 4 vs week 6
CEC (cells/mL)	6.5	17.75^c	6.12^d	0.03	0.85	0.64
VEGF (pg/mL)	360.67	217.19	167.66	0.07	0.03	0.004
VEGFR1 (pg/mL)	109.32	149.33	117.35	1.0	0.30	0.50
VEGFR2 (pg/mL)	1856.1	1264	1393.1	0.0002	0.004	0.03
VEGFR3 (ng/mL)	45.04	15.38	23.66	0.0002	0.004	0.004
Endoglin (ng/mL)	3.69	3.23	3.34	0.01	0.004	0.82
TIE-2 (ng/mL)	20.77	15.48	17.42	0.0002	0.004	0.03
VCAM-1 (ng/mL)	576.6	932.18	932.18	0.006	0.04	0.73
Angiopoeitin-2 (pg/mL)	2841.4	1537.2	1843.8	0.0002	0.004	0.04
MMP-9 (ng/mL)	609.3	312.8	363.6	0.01	0.03	0.25
CXCL-10 (pg/mL)	124.2	347.41	154.51	0.01	0.20	0.04
Prokineticin-1 (ng/mL)	0.615	0.646	0.54	0.22	1.0	0.57
Prokineticin-2 (pg/mL)	0.35	3.95	0.83	0.01	0.11	0.43
S100A9 (ng/mL)	3.26	2.55	2.8	0.64	0.10	0.73

^a Unless otherwise noted; ^bWilcoxon signed rank test; ^cn = 11; ^dn = 10.

Figure 2. Study schema: Patients received sunitinib 37.5 mg PO daily from weeks 1–4 and bevacizumab (Bev) 5 mg/kg intravenously on days 1, 15, and 29 of each 6-wk cycle.