Both phase II studies – Study 6 and Study 3 – met their primary endpoint of increased progression free survival (PFS) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).
Study 6 evaluated PFS with ZD6474 100mg or 300mg compared to placebo in 127 patients with advanced NSCLC receiving standard chemotherapy treatment with docetaxel after failure of first-line platinum-based chemotherapy. Results showed that adding ZD6474 100mg or 300mg to docetaxel increased median PFS to 19 weeks and 17 weeks, respectively, compared with 12 weeks for docetaxel plus placebo.
Furthermore, exploratory subgroup analyses suggested advantages in PFS for ZD6474 plus docetaxel compared with docetaxel plus placebo both for adenocarcinoma and for other lung cancer histologies, including squamous carcinoma.
A second, two-part trial, Study 3, compared the anti-tumour effects of ZD6474 300mg monotherapy with gefitinib (AstraZeneca’s Iressa) 250mg monotherapy in 168 patients with advanced NSCLC after the failure of first and/or second line chemotherapy.
In part A of the study, patients receiving ZD6474 300mg had a significant prolongation of PFS compared with gefitinib 250mg with a mean PFS of 11.9 weeks compared to 8.1 weeks, respectively.
Furthermore disease control for more than eight weeks was achieved in 45% of patients receiving ZD6474 and in 34% of those receiving gefitinib.
In part B, where eligible patients had the option to switch to the alternative treatment, disease control for more than eight weeks was achieved in 43% of patients who switched to ZD6474 (from gefitinib) and in 24% of those who switched to gefitinib (from ZD6474).
In both Study 3 and Study 6, there was no significant effect of ZD6474 on overall survival – possibly due to the small number of patients involved and the fact that survival data was potentially confounded by subsequent therapies. Both progression free survival and survival outcomes will be investigated in phase III trials.
The announcement of these new data follows the start of enrolment into the first phase III study with ZD6474 in advanced NSCLC, which is expected to enroll more than 1,200 patients worldwide.