SAN ANTONIO—Pilot studies presented at the 2007 San Antonio Breast Cancer Symposium have found robust activity for the multi-targeted tyrosine kinase inhibitor sunitinib (Sutent) when given with docetaxel (Taxotere) (abstract 6079) or paclitaxel (abstract 6078) as first-line treatment for patients with advanced breast cancer.
European investigators evaluated the pharmacokinetic profile, safety, and preliminary efficacy of sunitinib plus docetaxel in 22 advanced breast cancer patients. Docetaxel 75 mg/m2 was given on day 1 every 3 weeks and sunitinib 37.5 mg/d was started on day 2 and given for 2 weeks, followed by 1 week off.
When docetaxel was discontinued for reasons other than progressive disease, patients received continuous dosing with sunitinib, with treatment breaks and dose reductions as needed for tolerability concerns. Sunitinib doses were escalated to 50 mg/d if well tolerated. Patients received a median of eight cycles of sunitinib and six of docetaxel.
Of 18 evaluable patients, 13 (72.2%) responded (all partial responders), and 5 patients (27.7%) achieved stable disease. Nine patients experienced tumor shrinkage after just two cycles of therapy, several of whom had visceral disease. Five of six patients with triple-negative tumors (negative for estrogen and progesterone receptors and HER2 overexpression) responded, reported Luca Gianni, MD, of the Istituto Nazionale Tumori, Milan, Italy, lead author of the study.
Treatment with the combination was generally well tolerated. The most commonly reported severe adverse event was grade 4 transient neutropenia, which occurred in 11 patients (50%). Grade 3 adverse events were few and included one case each of fatigue, diarrhea, stomatitis, and hand-foot syndrome. Eleven patients discontinued treatment because of lack of efficacy (5), non-treatment-related reasons (4), and toxicity (2).
Co-investigator Gabriella Mariani, MD, commented that the good tolerability allows for sunitinib to be continued indefinitely without a problem.
“We can usually give full doses, and it is also possible to increase the dose of sunitinib,” Dr. Mariani said. “We now have one patient continuing on sunitinib after 12 cycles—6 on the combined regimen and 6 with single-agent sunitinib. Last week we evaluated her and the disease was still stable, after a good response. We have seen some fairly dramatic responses.”
A phase III study of this combination compared with docetaxel alone in the first-line metastatic setting is underway.