The negative trials don't get a lot of discussion, but the ZEPHYR trial, a phase III study that directly compared Zactima (vandetanib), an oral inhibitor of EGFR and angiogenesis, vs. placebo, was one that merits some follow-up after my reporting that it failed to show a survival benefit, which was essentially the only thing we learned about the trial prior to ASCO this year.
It's been a while since there was anything to discuss about Zactima (vandetanib), an oral targeted therapy being investigated by AstraZeneca that has the potential to inhibit both the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF), key targets of two important pathways in cancer treatment.
AstraZeneca (AZ) just issued a press release noting that they are withdrawing their application for the "multi-kinase inhibitor" Zactima (vandetanib) to receive FDA approval to be given along with chemo in advanced NSCLC right now.
Member Neil Berch just wrote a nice summary of the four large randomized clinical trials being done with Zactima (vandetanib), an oral targeted therapy that can block both the VEGF (angiogenic) and EGFR pathways. In fact, the name vandetanib comes from blocking V and E.
This post will be a little different from most of the expert posts on GRACE. I’m not an expert. I’m not an oncologist. In fact, I’m not a physician. I’m a patient with a social science background, and I’ve followed the work on the drug I’m writing about for some time. I’ve been interested in Zactima (vandetanib) for two reasons. First, I thought the early trials looked promising, and it might eventually be a drug that could help me. Second (and this is going to drive Dr. West crazy), the four large phase III trials of Zactima have really catchy acronyms (see below).
As a general rule, companies don't sit on great news with their drugs. Without any insider knowledge, this was my concern about why we hadn't heard anything about the results of three major lung cancer trials with the agent Zactima (vandetanib), which I had written a post about 8 months ago (see prior post about these trials with Zactima, an oral agent that inhibits both VEGF, a major mediator of angiogenesis, and the EGFR pathway).
There's been several discussions about the potential value of maintenance therapy after the initial chemotherapy for SCLC; I've discussed this subject in a prior post, in which I focused on chemo -- while the results haven't been strong enough to lead to a change in standard practice, at least one trial showed a strong trend in the right direction.
As introduced in the last post, ZD6474, or Zactima, is a pill that blocks tumor blood supply and at higher doses (in the 300 mg per day range) also blocks EGFR. This mutli-targeted therapy has shown some intriguing activity when combined with chemo, and today I'll focus on the research that gave it as a single agent and where it has led us in terms of current trials.
In prior posts I've described the idea of combining targeted agents like Tarceva and Avastin, but there are also some single agents that inhibit multiple targets within cancer cells. I've described sorafenib/nexavar in a prior post. Today I'll focus on another multi-targeted agent, known previously as ZD6474, and with a marketing name of Zactima. Similar to the combination of avastin and tarceva, this single oral drug is anti-angiogenic and also blocks EGFR. Although less well studied, it also blocks a protein called RET and can inhibit cell proliferation that way.