ASCOThe future of breast cancer therapies will involve agents targeting multiple aspects of the signaling pathway. At ASCO 2007, investigators reported encouraging preliminary activity for numerous agents in the pipeline.
In an effort to treat HER2-positive patients who progress after trastuzumab (Herceptin)and, in general, to find effective alternatives to trastuzumab in this patient subsetinvestigators are evaluating a number of HER2-targeted agents.
One of these is a second-generation heat shock protein 90 inhibitor, alvespimycin (Kosan Biosciences). The drug can disrupt the activity of multiple oncogenes and cell signaling pathways implicated in tumor growth, including HER2.
In a phase I trial (abstract 1115), 25 very heavily pretreated patients with HER2-positive metastatic disease received 1-hour weekly infusions of alvespimycin plus trastuzumab. The median number of prior regimens excluding hormone therapy was 6.5; the median prior trastuzumab-containing regimens was 4.
Clinical benefit was observed in 35% of patients; 5 patients had prolonged stabilization for 4, 5, 6+, 11+, and 12 months.
One patient, who had 13 prior regimens, including progression on single-agent lapatinib (Tykerb) and 3 prior trastuzumab-containing regimens, had almost complete resolution of lung me-tastases. One patient with 11 prior regimens showed a 10% reduction in tumor mass and a decrease in two tumor markers, and is continuing on the study.
One ovarian cancer patient with 13 prior regimens remained on study for over 16 months and had a near complete resolution of ascites and left pleural effusion, and an 83% decrease in CA125.