Earlier this year, Pfizer cancelled two major phase III trials in breast cancer involving their multi-kinase inhibitor, Sutent (sunitinib). SUN 1107 evaluated
single-agent sunitinib versus single-agent capecitabine for the treatment of a
broad range of patients with advanced breast cancer after failure of standard
treatment. In addition, SUN 1094,
a Phase 3 study, evaluated Sutent plus paclitaxel versus
bevacizumab plus paclitaxel for the first line treatment of patients with
advanced breast cancer.
In both cases, the independent Data Monitoring Committee (DMC) found
that if treatment with sunitinib continued, it would be unable to meet the
primary endpoint of superior progression-free survival (PFS).
Imagine the surprise of many then, when a Reuters press release hit the wires today stating:
"Nexavar, when combined with standard chemotherapy Xeloda, helped keep tumours in check for longer than in a control group of patients receiving Xeloda only, the drugmakers said in a joint statement on Wednesday, citing data from a Phase II study."
Wow, what a wild ride R&D is sometimes.
What's common about these two drugs? Well, they both inhibit multiple kinases, including VEGF, and both were tested in combination with capecitabine in breast cancer. It should be noted however, that Sutent showed similar promise in phase II, only for the phase III interim analysis to be resoundingly negative. It will be interesting to see how Nexavar fares, because there are no guarantees that the large scale trials will support the earlier data, as Pfizer found.
It is possible that Bayer/Onyx chose a different population of women with breast cancer. My eye was drawn to a hidden snippet in the press release that said:
"The trial involved 229 women with breast tumours that had started spreading."
This is important to note because the mechanism of action for VEGF inhibitors is via anti-angiogenesis when the tumours are sizeable enough that they need to grow by increased blood vessels and vascularisation. In the recent adjuvant colorectal trials looking at FOLFOX plus Avastin, it was clear that while Avastin
(another VEGF inhibitor) worked in metastatic disease, it has significantly less value in the earlier setting before the tumour begins to vascularise.
It is therefor possible that the women in the Bayer/Onyx trial may be at a slightly later stage of tumour growth than the women in the Pfizer trials, which would likely make a better target for a VEGF inhibitor. I wonder. We shall see if this hypothesis is correct as more details emerge over the next 18 months.