were randomised to platinum-based chemotherapy (paclitaxel 200 mg/m2) and carboplatin AUC = 6.0, both by IV infusion (PC) on day 1 of every 3-week cycle for up to 6 cycles or PC in combination with Avastin at a dose of 15 mg/kg IV infusion day 1 of every 3-week cycle. After completion of six cycles of carboplatin-paclitaxel chemotherapy or upon premature discontinuation of chemotherapy, patients on the Avastin + carboplatin–paclitaxel arm continued to receive Avastin as a single agent every 3 weeks until disease progression. 878 patients were randomised to the two arms.
During the trial, of the patients who received trial treatment, 32.2% (136/422) of patients received 7-12 administrations of Avastin and 21.1% (89/422) of patients received 13 or more administrations of Avastin.
The primary endpoint was duration of survival. Results are presented in Table 12.
Table 12 Efficacy results for trial E4599
Arm 1
Carboplatin/Paclitaxel
Arm 2
Carboplatin/ Paclitaxel + Avastin
15 mg/kg q 3 weeks
Number of patients
444
434
Overall survival
Median (months)
10.3
12.3
Hazard ratio
0.80 (p=0.003)
95% CI (0.69; 0.93)
Progression-free survival
Median (months)
4.8
6.4
Hazard ratio
0.65 (p < 0.0001)
95% CI (0.56; 0.76)
Overall response rate
Rate (percent)
12.9
29.0 (p < 0.0001)
In an exploratory analysis, the extent of Avastin benefit on overall survival was less pronounced in the subgroup of patients who did not have adenocarcinoma histology.
BO17704
Trial BO17704 was a randomised, double-blind phase III trial of Avastin in addition to cisplatin and gemcitabine versus placebo, cisplatin and gemcitabine in patients with locally advanced (stage IIIb with supraclavicular lymph node metastases or with malignant pleural or pericardial effusion), metastatic or recurrent non-squamous NSCLC, who had not received prior chemotherapy. The primary endpoint was progression free survival, secondary endpoints for the trial included the duration of overall survival.
Patients were randomised to platinum-based chemotherapy, cisplatin 80 mg/m2 intravenous infusion on day 1 and gemcitabine 1250 mg/m2 intravenous infusion on days 1 and 8 of every 3-week cycle for up to 6 cycles (CG) with placebo or CG with Avastin at a dose of 7.5 or 15 mg/kg IV infusion day 1 of every 3-week cycle. In the Avastin-containing arms, patients could receive Avastin as a single-agent every 3 weeks until disease progression or unacceptable toxicity. Trial results show that 94% (277 / 296) of eligible patients went on to receive single agent bevacizumab at cycle 7. A high proportion of patients (approximately 62%) went on to receive a variety of non-protocol specified anti-cancer therapies, which may have impacted the analysis of overall survival.
The efficacy results are presented in Table 13.
Table 13 Efficacy results for trial BO17704
Cisplatin/Gemcitabine + placebo
Cisplatin/Gemcitabine + Avastin
7.5 mg/kg q 3 weeks
Cisplatin/Gemcitabine + Avastin
15 mg/kg q 3 weeks
Number of patients
347
345
351
Progression-free survival
&
