Pfizer's Sutent fails first Phase III breast cancer trial
This article was originally published in Scrip
Pfizer's Sutent (sunitinib) has been dealt a significant blow after failing its first Phase III trial in advanced breast cancer, but the company will continue other Phase III trials in the disease, it said.
Sutent, a multi-targeted kinase inhibitor, is one of Pfizer's biggest cancer drug hopes, with the most robust and advanced development programme, after it succeeded in renal cell carcinoma (kidney cancer). It is also approved for second-line use in rare gastrointestinal stromal tumours (GIST). Sutent now appears to be the most commonly prescribed first-line treatment in RCC and last year had sales of $847 million.
Pfizer is hoping to win approval for the drug in the major tumour types which cause the most cancer-related deaths in the western world: lung cancer, breast cancer, colorectal cancer and prostate cancer. Sutent is in Phase III trials for each of these indications, as well as liver cancer, and in Phase II trials in a number of other tumour types.
In RCC, it is thought to work because it targets the VEGF receptors which are involved in angiogenesis; kidney cancer is known as one of the most angiogenic tumour types. Another of its targets is the protein kinase KIT, whose mutation has been identified as one of the major causes of GIST.
As all tumours are reliant to some degree on angiogenesis, or the growth of new blood vessels, Sutent could potentially have an effect on many cancers, including breast. So far, Roche/Genentech's VEGF inhibitor Avastin (bevacizumab) is the only anti-angiogenic drug that has gained approval for advanced breast cancer. In the US, Avastin gained an accelerated approval, but the FDA's decision was controversial as it had failed to demonstrate an overall survival benefit although it delayed disease progression (improved progression-free survival).
Sutent's Phase III breast cancer trial, SUN 1107, had enrolled 455 patients, or about 65% of the planned number, Pfizer told Scrip. It evaluated sunitinib versus capecitabine (Roche's oral chemotherapy drug Xeloda) for the treatment of a broad range of patients with advanced breast cancer who had failed standard treatment.
An independent data monitoring committee (DMC) found that even if the trial had been allowed to continue, treatment with Sutent would be unable to demonstrate a statistically significant improvement in the primary endpoint of progression-free survival (PFS). Data are currently being analysed.
"We are disappointed with these results given the previous findings that suggested sunitinib may provide benefit for patients with this difficult-to-treat cancer," said Dr Mace Rothenberg, senior vice-president of clinical development and medical affairs for Pfizer’s oncology business unit. "In ongoing studies, we remain committed to evaluating sunitinib in advanced breast cancer and are continuing to study sunitinib in different populations and with different regimens."
Sutent is in three other Phase III trials in advanced breast cancer. One, SUN 1094, is comparing Sutent with Avastin, both in combination with paclitaxel chemotherapy, in the first-line setting. PFS is the primary endpoint.
Another first-line trial, SUN 1064, is comparing Sutent in combination with docetaxel chemotherapy with docetaxel alone. PFS is the primary endpoint, and data on this could come as soon as August.
Finally, another Phase III trial, in previously treated patients, is comparing Sutent in combination with capecitabine with capecitabine alone.