Clinical outcome with bevacizumab in patients with recurrent high-grade glioma treated outside clinical trials

Figures & data

Table I. Common treatment regimens for recurrent glioblastomas.

	NABTC Phase II [4]	TMZ 7/7 [16]	CCNU [15]	BEV [11]	BEV/CPT-11 [11]
Number of patients (n)	437*	64*	92	85	82
Median age (years)	52 (21–84)	51	55.3	54 (23–78)	57 (23–78)
KPS (%)
90–100	40	72	49	44.7	37.8
70–80	54	–	50	55.3	62.2
In first relapse (%)	50	–	77	81.2	80.5
Time from diagnosis to treatment (months)	–	8.5	12	8.6	9.8
Median duration of response (months)	–	–	2.8–9.6	5.6	4.3
Median PFS (months)	1.6/3.4**	5.5	1.64	4.2	5.6
Median OS (months)	6/7**	8.7	7.1	9.2	8.7

*Patient cohort with grade IV tumors; **Non-temozolomide/temozolomide regimen, respectively.

NABTC, North American Brain Tumor Consortium; TMZ 7/7 temozolomide one week on, one week off; CCNU, lomustine; BEV, bevacizumab; CPT-11, irinotecan; KPS, Karnofsky Performance Score; PFS, progression-free survival; OS, overall survival.

Table II. Patient demographics.

	Glioblastoma	Other HGG	All
Number of patients, n (%)	176 (100)	49 (100)	225 (100)
Gender, n (%)
Male	107 (60.8)	30 (61.2)	137 (60.9)
Female	69 (39.2)	19 (38.8)	88 (39.1)
Age (years)
Median	55	46	52
Range	19–79	20–70	19–79
Median time from initial diagnosis to start of BEV, days (months)	305 (10.0)	1328 (43.5)	335 (11.0)

HGG, high-grade glioma (anaplastic astrocytoma, oligodendroglioma and mixed glioma); BEV, bevacizumab.

Table III. Changes in KPS and corticosteroid use in patients prior to and during BEV.

	Glioblastoma (n = 176)	Other HGG (n = 49)	All (n = 225)
Steroids at start of treatment, n (%)
Yes	123 (69.9)	26 (53.1)	149 (66.2)
No	42 (23.9)	15 (30.6)	57 (25.3)
Missing	11 (6.2)	8 (16.3)	19 (8.5)
Steroid interruption during treatment, n (%)
Yes	48 (27.3)	8 (16.3)	56 (24.9)
No	73 (41.5)	17 (34.7)	90 (40.0)
Not applicable* or missing	55 (31.2)	24 (49.0)	79 (35.1)
KPS prior to treatment, n (%)
I (80–100)	69 (39.2)	21 (42.9)	90 (40.0)
II (60–70)	63 (35.8)	13 (26.5)	76 (33.8)
III (<60)	30 (17.1)	9 (18.4)	39 (17.3)
Missing	14 (8.0)	6 (12.2)	20 (8.9)
KPS change during treatment, n (%)
Improved	20 (11.4)	3 (6.1)	23 (10.2)
Stable	120 (68.1)	34 (69.4)	154 (68.4)
Worse	16 (9.1)	4 (8.2)	20 (8.9)
Missing	20 (11.4)	8 (16.3)	28 (12.5)

HGG, high-grade glioma (anaplastic astrocytoma, oligodendroglioma and mixed glioma); KPS, Karnofsky Performance Score, BEV bevacizumab.

*not applicable, where no steroids at start of BEV treatment.

Table IV. Duration of BEV treatment.

	Glioblastoma (n = 176)	Other HGG (n = 49)	All (n = 225)
Duration of BEV treatment (months)
Median	5.45	6.2	5.5
Range	0.5–39	0.5–36	0.5–39
Patients on treatment, n (%)
≥6 months	86 (48.9)	25 (51.0)	111 (49.3)
≥1 year	31 (17.6)	12 (24.5)	43 (19.1)
≥2 year	6 (3.4)	4 (8.2)	10 (4.4)

HGG, high-grade glioma (anaplastic astrocytoma, oligodendroglioma and mixed glioma); BEV, bevacizumab.

Table V. Overall survival in HGG patients treated with BEV at recurrence.

	Glioblastoma (n = 176)	Other HGG (n = 49)	All (n = 225)
OS from start of BEV treatment, days
Median, days (months)	252 (8.3)	277 (9.1)	259 (8.5)
95% CI	216; 305	190; 372	224; 305
OS from diagnosis
Median, days (months)	668 (21.9)	1972 (64.7)	732 (24.0)
95% CI	569; 762	890; 3485	660; 846

HGG; high-grade glioma (anaplastic astrocytoma, oligodendroglioma and mixed glioma); BEV, bevacizumab; OS, overall survival; CI, confidence interval.

Figure 1. Overall survival from beginning of bevacizumab (BEV) treatment.

Table VI. Reasons for discontinuation of BEV treatment.

	All (n = 225)
Progression (total PD), n (%)	171 (76.0)
Clinical PD	33 (14.7)
Radiological PD	38 (16.9)
Clinical and radiological PD	100 (44.4)
Toxicity, n (%)	21 (9.3)
Toxicities that led to death (fatal)	5 (2.2)
CNS bleeding (3 fatal, included above)	6 (2.6)
Bleeding other location	2 (0.8 )
Wound-healing complications (2 fatal, included above)	5 (2.2)
Thromboembolism (venous or arterial)	4 (1.7)
Hand-foot syndrome^‡	1 (0.4)
Proteinuria	2 (0.8)
Diarrhea^¥	1 (0.4)
Other reasons, n (%)	24 (10.6)
Not assessed	9 (4.0)
Patient wish	11 (4.8)
Sustained tumor response	4 (1.7)

PD, progressive disease.

*Multiple reasons for BEV discontinuation were possible.

‡Bevacizumab combined with pegylated liposomal doxorubicin.

¥Bevacizumab with irinotecan.

Lamborn KR, Yung WK, Chang SM, Wen PY, Cloughesy TF, DeAngelis LM, . Progression-free survival: An important end point in evaluating therapy for recurrent high-grade gliomas. Neuro Oncol 2008;10:162–70.

 PubMed Web of Science ®Google Scholar

Wick A, Felsberg J, Steinbach JP, Herrlinger U, Platten M, Blaschke B, . Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma. J Clin Oncol 2007; 25:3357–61.

 PubMed Web of Science ®Google Scholar

Wick W, Puduvalli VK, Chamberlain MC, van den Bent MJ, Carpentier AF, Cher LM, . Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol 2010;28: 1168–74.

 PubMed Web of Science ®Google Scholar

Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, . Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009; 27:4733–40.

 PubMed Web of Science ®Google Scholar