Pfizer is slashing three late-stage cancer programs, namely two Sutent trials in advanced Her-2 negative breast cancer and figitumumab as a second/third-line treatment for nonadenocarcinoma non-small-cell lung cancer (NSCLC). These are not the first Phase III trials that have been halted for these candidates, which have been plagued by negative study results, slowing their advancement as therapies for multiple cancer types.
Pfizer reported that data from two Phase III studies of Sutent in advanced breast cancer failed to show progression-free survival. Additionally, there were more adverse events including serious adverse events in the investigational arm than in the comparator arm of each study. The SUN 1064 Phase III study involved Sutent in combination with docetaxel as a first-line treatment, and the SUN 1099 Phase III study compared Sutent plus capecitabine in previously treated advanced breast cancer patients.
The decision to stop the Phase III figitumumab study (A4021018) was based on the independent data safety monitoring committee’s (DSMC’s) finding that the trial was unlikely to demonstrate a statistically significant improvement in the primary endpoint of overall survival. The firm was evaluating figitumumab in combination with erlotinib as a second/third-line treatment for patients with previously treated nonadenocarcinoma NSCLC.
Pfizer has been forced to halt one Phase III trial with figitumumab and three Phase III studies with Sutent, which is already marketed for gastrointestinal stromal tumors after disease progression on or intolerance to imatinib mesylate and advanced/metastatic renal cell carcinoma.
The last figitumumab trial was called off in December 2009, after an analysis by the DSMC showed that addition of figitumumab to carboplatin plus paclitaxel as a first-line treatment would be unlikely to meet the primary endpoint of improved overall survival for patients with advanced nonadenocarcinoma NSCLC. In September 2009, the DSMC stopped new patient enrollment after observing an increase in serious adverse events including deaths in the treatment arm.
After its decision to nix the trial entirely, Pfizer said that it would try to identify a subset of NSCLC patients who would benefit from the addition of figitumumab to chemotherapy. Figitumumab is a fully human mAb targeting the insulin growth factor-1 receptor pathway. It is currently in Phase II trials in prostate, breast, and lung cancers as well as Ewing’s sarcoma.
Sutent’s three prior late-stage failures have been in breast and colorectal cancers. It did not show benefits as a single-agent for patients with advanced breast cancer who had failed prior treatment. Additionally, no advantages were seen in a trial evaluating Sutent along with paclitaxel as a first-line treatment in advanced breast cancer. And from today’s reports, it cannot be combined with docetaxel as a first-line treatment or capecitabine in previously treated advanced breast cancer patients either.
“Sunitinib has been thoroughly evaluated in advanced Her-2 negative breast cancer, and while we are disappointed in the results, these trials have helped us define the limits and opportunities for the compound and better understand the complex biology of this disease,” says Mace Rothenberg, M.D., svp of clinical development and medical affairs for Pfizer’s oncology business unit, in response to the most recent failure.
The colorectal cancer trial that previously failed compared Sutent plus Folfiri versus Folfiri alone for the first-line treatment of metastatic colorectal cancer. Pfizer’s only success with expanding Sutent’s label came in June 2009, when the firm reported that patients with advanced neuroendocrine-type pancreatic islet cell tumors treated with the compound had a median progression-free survival of 11.1 months compared to those on placebo who had a PFS of 5.5 months.
Pfizer says that it will forge ahead with evaluating Sutent in other solid tumors including advanced NSCLC, advanced castration-resistant prostate cancer, advanced hepatocellular carcinoma, and as adjuvant therapy for renal cell carcinoma, all in Phase III trials.
Sutent is an oral multikinase inhibitor that works by blocking multiple molecular targets implicated in the growth, proliferation, and spread of cancer, according to Pfizer. Key Sutent targets include vascular endothelial growth factor receptor and platelet-derived growth factor receptor.
In February 2009, Pfizer reported another late-stage cancer trial failure involving axitinib as a treatment of advanced pancreatic cancer. In April 2008, Pfizer also shut down its Phase III melanoma trial with tremelimumab, which was licensed from Medarex. In January of this year, however, Pfizer signed on Debiopharm to conduct late-stage studies with the candidate using a biomarker that was identified to predict patients who were more likely to respond.