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Positive Phase 2 Results Spur Zactima Phase 3 Trials To Begin in the Fall
Trial 003 compared the anti-tumor effects of ZACTIMA 300 mg monotherapy with gefitinib monotherapy, in patients with advanced non-small-cell lung cancer (NSCLC) after failure of first and/or second-line platinum-based chemotherapy. Preliminary results from Trial 003 showed that patients receiving ZACTIMA had an estimated median time to progression (TTP) of 11.9 weeks compared to a TTP with gefitinib of 8.1 weeks (HR 0.63; 95% CI 0.44 to 0.90; p=0.011). Notable adverse event profile observed with ZACTIMA monotherapy (NIH common toxicity criteria greater than or equal to grade 3) included rash (2.4%) and diarrhea (7.2%).
Lead Trial 003 investigator, Ron Natale MD, Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA, commented, "ZACTIMA targets two established pathways in tumor growth - EGF and VEGF, an approach which tackles two different processes at the same time."
As combination therapy, Trial 006, showed patients with previously treated advanced NSCLC receiving ZACTIMA 100mg plus docetaxel had a median TTP of 18.7 weeks (HR 0.64; 95% CI 0.38 to 1.05; p=0.074), and patients receiving ZACTIMA 300mg plus docetaxel had a median TTP of 17.0 weeks (HR 0.83; 95% CI 0.50 to 1.36; p=0.416). The median TTP of the docetaxel alone group was 12.0 weeks. Side effects in the ZACTIMA 100mg + docetaxel group was similar to those observed in patients treated with docetaxel alone. Notable side effects in the ZACTIMA 300mg + docetaxel group (NIH common toxicity criteria greater than or equal to grade 3) included rash (18.2%) and diarrhea (13.6%).
"Given the poor prognosis in lung cancer, an increase in time to progression can be meaningful for these patients," said Trial 006 principal investigator Roy Herbst MD, PhD, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. "The results of Trials 003 and 006, as both a monotherapy and in combination with chemotherapy, provide encouraging support warranting Phase III investigation with ZACTIMA."
Due to the small number of patients involved, and the fact that survival data was potentially confounded by subsequent therapies, further assessment of survival outcomes will be investigated in Phase III trials. There was no significant effect of ZACTIMA on overall survival.
In both studies, treatment with ZACTIMA was associated with asymptomatic QT prolongation.
Further Phase II data for ZACTIMA at WCLC
Preliminary results from the run-in phase of Trial 007 evaluating the combination of ZACTIMA and carboplatin/paclitaxel (CP) chemotherapy as a first-line treatment for patients with advanced or metastatic NSCLC compared to ZACTIMA alone and CP alone were also presented. The randomized phase of the study to evaluate objective tumor response and provide pharmacokinetic assessment of ZACTIMA and carboplatin levels is ongoing.