Phase IIIb study of the bevacizumab biosimilar candidate BI 695502 plus mFOLFOX6 in metastatic colorectal cancer

Figures & data

Figure 1. Patient disposition (CONSORT diagram).

AE: Adverse event.

Table 1. Patient demographics and baseline characteristics.

Parameter	Patients treated with BI 695502 (N = 123)
Age, median (range), years	59 (22–85)
Age group, n (%)
<65 years	81 (65.9)
≥65 years	42 (34.1)
Gender, n (%)
Male	68 (55.3)
Female	55 (44.7)
Race, n (%)
Asian	33 (26.8)
Black/African–American	6 (4.9)
Caucasian	82 (66.7)
Other	2 (1.6)
Time since initial diagnosis, median (range), months	1.6 (0.0–105.7)
Stage of cancer at diagnosis, n (%)
I	2 (1.6)
II	11 (8.9)
III	10 (8.1)
IV	100 (81.3)
ECOG PS at baseline, n (%)
0	67 (54.5)
≥1	55 (44.7)
Missing	1 (0.8)
RAS status at baseline, n (%)
Wild-type	71 (57.7)
Mutated	50 (40.7)
Missing	2 (1.6)
Histology at baseline, n (%)
Adenocarcinoma	118 (95.9)
Mucinous (colloid) adenocarcinoma	2 (1.6)
Adenosquamous carcinoma	1 (0.8)
Other	2 (1.6)

ECOG PS: Eastern Cooperative Oncology Group performance status.

Table 2. Primary safety analysis: number and proportion of patients with prespecified adverse events.

AE category Preferred term	Patients treated with BI 695502 (N = 123)
	n [events]	Incidence (%) [95% CI ^† ]
Any prespecified AE included in the primary end point assessment	72 [179]	58.5 [49.70–66.86]
Anaphylactic, hypersensitivity or infusion-related reaction	23 [37]	18.7 [12.80–26.50]
Drug hypersensitivity	7 [8]	5.7 [NC]
Arterial and venous thromboembolic events	15 [20]	12.2 [7.53–19.15]
Pulmonary embolism	6 [6]	4.9 [NC]
Gastrointestinal perforations	3 [3]	2.4 [0.83–6.93]
Hypertension	35 [56]	28.5 [21.23–36.99]
Proteinuria	12 [16]	9.8 [5.67–16.28]
Hemorrhage	28 [46]	22.8 [16.25–30.93]
Epistaxis	18 [22]	14.6 [NC]
Rectal hemorrhage	6 [6]	4.9 [NC]
Wound-healing complications/abscess/fistulas	2 [2]	1.6 [0.45–5.74]
Posterior reversible encephalopathy syndrome	0 [0]	0 [0.00–3.03]
Ovarian failure	0 [0]	0 [0.00–6.53]

† CI determined using the Wilson score method for AE categories.

AE: Adverse event; CI: Confidence interval; NC: Not calculated.

Figure 2. Subgroup analyses of the primary end point (percentages of patients with at least one of the prespecified adverse events).

^†Confidence interval determined using Wilson score method.

CI: Confidence interval; ECOG PS: Eastern Cooperative Oncology Group performance status.

Table 3. Adverse events occurring during the study.

All adverse events ^†		Adverse events related to study treatment ^‡
Number of patients with ≥1 adverse event (N = 123)	121 (98.4)	Patients with ≥1 treatment-related adverse event (N = 123)	89 (72.4)
Nausea	57 (46.3)	Hypertension	25 (20.3)
Fatigue	45 (36.6)	Fatigue	21 (17.1)
Peripheral sensory neuropathy	44 (35.8)	Epistaxis	16 (13.0)
Diarrhea	41 (33.3)	Nausea	16 (13.0)
Stomatitis	37 (30.1)	Diarrhea	15 (12.2)
Hypertension	34 (27.6)	Neutropenia	13 (10.6)
Neutropenia	32 (26.0)	Decreased appetite	13 (10.6)
Constipation	27 (22.0)	Constipation	11 (8.9)
Decreased appetite	26 (21.1)	Stomatitis	9 (7.3)
Neutrophil count decreased	25 (20.3)	Thrombocytopenia	7 (5.7)
Neuropathy peripheral	21 (17.1)	Dysgeusia	7 (5.7)
Anemia	21 (17.1)	Proteinuria	7 (5.7)
Thrombocytopenia	20 (16.3)	Peripheral sensory neuropathy	6 (4.9)
Vomiting	20 (16.3)	Headache	6 (4.9)
White blood cell count decreased	18 (14.6)	Vomiting	6 (4.9)
Platelet count decreased	18 (14.6)	Rhinorrhea	5 (4.1)
Dysgeusia	18 (14.6)	Abdominal pain	5 (4.1)
Weight decreased	18 (14.6)	Pyrexia	5 (4.1)
Epistaxis	18 (14.6)	Weight decreased	5 (4.1)
Pyrexia	17 (13.8)	Neuropathy peripheral	4 (3.3)
Abdominal pain	17 (13.8)	Paresthesia	4 (3.3)
Alopecia	16 (13.0)	Dyspnea	4 (3.3)
Headache	14 (11.4)	Malaise	4 (3.3)
		Neutrophil count decreased	4 (3.3)

† Adverse events affecting >10% of treated patients are presented.

‡ Treatment-related adverse events affecting ≥3% of treated patients are presented.

Figure 3. Kaplan–Meier curves.

(A) PFS assessed by central imaging review and (B) overall survival.

CI: Confidence interval; OS: Overall survival; PFS: Progression-free survival.

Figure 4. Preinfusion plasma concentrations over time.

Data shown are the median (horizontal line) within the 25th percentile to 75th percentile box, geometric mean (square) and mean (diamond). The range shown by the ‘whiskers’ is defined by the 25th percentile minus 1.5-times the interquartile range (IQR) and the 75th percentile plus 1.5-times the IQR. Circles represent outlying results.

BLQ: Below the limits of quantification.

Data sharing statement

The authors certify that this manuscript reports original clinical trial data: NCT02776683/2015-003718-25. To ensure independent interpretation of clinical study results and enable authors to fulfill their role and obligations under the ICMJE criteria, Boehringer Ingelheim grants all external authors access to relevant clinical study data pertinent to the development of the publication. In adherence with the Boehringer Ingelheim Policy on Transparency and Publication of Clinical Study Data, scientific and medical researchers can request access to clinical study data after publication of the primary manuscript in a peer-reviewed journal, regulatory activities are complete and other criteria are met. Researchers should use the https://vivli.org/ link to request access to study data and visit https://www.mystudywindow.com/msw/datasharing for further information.