3 95% CI for one sample binomial using Pearson-Clopper method

4 Approximate 95% CI for difference of two rates using Hauck-Anderson method

5 log-rank test (stratified)

6 Primary analysis was performed with a data cut-off date of 12 December 2012 and is considered the final analysis

7 Follow-up analysis was performed with a data cut-off date of 07 March 2014

8 p-value displayed for descriptive purpose only

Table 24 Overall survival results from study GOG-0240 by Trial Treatment

Treatment Comparison
 Other Factor
 Overall survival – Primary analysis1

Hazard Ratio (95% CI)
 Overall survival - Follow-up analysis2

Hazard Ratio (95% CI)
 
Avastin vs. No Avastin
 Cisplatin+ Paclitaxel
 0.72 (0.51, 1.02)

(17.5 vs.14.3 months; p = 0.0609)
 0.75 (0.55, 1.01)

(17.5 vs.15.0 months; p = 0.0584)
 
Topotecan+ Paclitaxel
 0.76 (0.55, 1.06)

(14.9 vs. 11.9 months; p = 0.1061)
 0.79 (0.59, 1.07)

(16.2 vs. 12.0 months; p = 0.1342)
 
Topotecan+ Paclitaxel vs. Cisplatin+ Paclitaxel
 Avastin
 1.15 (0.82, 1.61)

(14.9 vs. 17.5 months; p = 0.4146)
 1.15 (0.85, 1.56)

(16.2 vs 17.5 months; p = 0.3769)
 
No Avastin
 1.13 (0.81, 1.57)

(11.9 vs.14.3 months; p = 0.4825)
 1.08 (0.80, 1.45)

(12.0 vs 15.0 months; p = 0.6267)
 

1 Primary analysis was performed with a data cut-off date of 12 December 2012 and is considered the final analysis

2 Follow-up analysis was performed with a data cut-off date of 07 March 2014; all p-values are displayed for descriptive purpose only

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies, in all subsets of the paediatric population, in breast carcinoma, adenocarcinoma of the colon and rectum, lung carcinoma (small cell and non-small cell carcinoma), kidney and renal pelvis carcinoma (excluding nephroblastoma, nephroblastomatosis, clear cell sarcoma, mesoblastic nephroma, renal medullary carcinoma and rhabdoid tumour of the kidney), ovarian carcinoma (excluding rhabdomyosarcoma and germ cell tumours), fallopian tube carcinoma (excluding rhabdomyosarcoma and germ cell tumours), peritoneal carcinoma (excluding blastomas and sarcomas) and cervix and corpus uteri carcinoma.

Anti-tumour activity was not observed in two studies among a total of 30 children aged > 3 years old with relapsed or progressive high-grade glioma when treated with bevacizumab and irinotecan. There is insufficient information to determine the safety and efficacy of bevacizumab in children with newly-diagnosed high-grade glioma.

In a single-arm study (PBTC-022), 18 children with recurrent or progressive non-pontine high-grade glioma (including 8 with glioblastoma [WHO Grade IV], 9 with anaplastic astrocytoma [Grade III] and 1 with anaplastic oligodendroglioma [Grade III]) were treated with bevacizumab (10 mg/kg) two weeks apart and then with bevacizumab in combination with CPT-11 (125-350 mg/m2) once every two weeks until progression. There were no objective (partial or complete) radiological responses (MacDonald criteria). Toxicity and adverse reactions included arterial hypertension and fatigue as well as CNS ischaemia with acute neurological deficit.

In a retrospective sin