Novartis reported positive data from separate Phase III studies evaluating Afinitor® (everolimus) in patients with breast cancer and in patients with noncancerous kidney tumors associated with tuberous sclerosis complex (TSC).
The 724-patient global Bolero-2 study evaluated the addition of everolimus to exemestane in postmenopausal women with ER+Her2- advanced breast cancer whose disease had recurred or progressed despite previous treatment with letrozole or anastrozole. The results showed that in comparison with exemestane treatment alone, everolimus/exemestane combination therapy reduced the risk of progression by 57%, and at a preplanned analysis more than doubled progression free survival, to 6.9 months.
The improvement was consistent across all subgroups, including number of prior therapies, presence of visceral disease, bone metastases, and prior use of chemotherapy. Novartis says the Bolero-2 data will support worldwide regulatory submissions, which are planned for filing by the end of 2011.
The 118-patient Exist-2 study, meanwhile, was designed to evaluate use of everolimus in patients with TSC-angiomyolipoma. TSC is the genetic disorder that also causes subependymal giant cell astrocytoma (SEGA) in the brain, an indication for which everolimus has already been approved in selected markets including the U.S.
Data from the placebo-controlled Exist-2 study patients showed that treatment using everolimus led to a 42% response rate, assessed as a reduction of at least 50% from baseline in the cumulative volume of all target angiomyolipoma lesions, and absence of new lesions over one centimeter in diameter. Everolimus therapy also led to a 26% skin lesion response rate and significantly increased time to angiomyolipoma progression: while medium time to progression was 11.37 months for placebo patients, medium time to progression was not reached in the everolimus arm. Novartis says the Exist-2 results will be used to support worldwide regulatory filings to expand the current TSC-SEGA indication.