(95% CI)
 0.88 (0.69, 1.13)
 
p-value (exploratory)
 0.33

a1000 mg/m2 oral twice daily for 14 days administered every 3 weeks
bStratified analysis included all progression and death events except those where non-protocol therapy (NPT) was initiated prior to documented progression; data from those patients were censored at the last tumor assessment prior to starting NPT.

An unstratified analysis of PFS (investigator assessed) was performed that did not censor for non-protocol therapy prior to disease progression. The results of these analyses were very similar to the primary PFS results.

Non-small cell lung cancer (NSCLC)

The safety and efficacy of Avastin, in addition to platinum-based chemotherapy, in the first-line treatment of patients with non-squamous non-small cell lung cancer (NSCLC), was investigated in trials E4599 and BO17704. An overall survival benefit has been demonstrated in trial E4599 with a 15 mg/kg/q3wk dose of bevacizumab. Trial BO17704 has demonstrated that both 7.5 mg/kg/q3wk and 15 mg/kg/q3wk bevacizumab doses increase progression free survival and response rate.

E4599

E4599 was an open-label, randomised, active-controlled, multicentre clinical trial eva luating Avastin as first-line treatment of patients with locally advanced (stage IIIb with malignant pleural effusion), metastatic or recurrent NSCLC other than predominantly squamous cell histology.

Patients were randomized 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 10.
Table 10 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 (