Bristol To Submit Ixabepilone In First Half Of 2007 For Metastatic Breast Cancer
This article was originally published in The Pink Sheet Daily
Executive Summary
Firm reports statistically significant Phase III data for ixabepilone/Xeloda combination at American Society of Clinical Oncology meeting in Chicago.
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Bristol-Myers Squibb's investigational chemotherapy agent ixabepilone demonstrated superior efficacy in a highly resistant metastatic breast cancer population when used in combination with capecitabine (Roche's Xeloda ), Bristol reported at the American Society of Clinical Oncology meeting in Chicago June 3. Bristol plans to file the NDA for the novel chemotherapy agent by the end of the first half, the firm told "The Pink Sheet" DAILY. "Not only is there an improvement in progression-free survival, but there is a 2.5 fold increase in the overall response rate, and this benefit was seen across most groups," principal investigator Linda Vahdat, Weill Cornell Medical College, said at ASCO. The therapy also has a "manageable safety profile in the presence of normal or mild hepatic dysfunction," Vahdat said. The study protocol was amended in response to a higher number of deaths in the combination group among patients with liver metastasis, Vahdat explained. Of 14 treatment-related deaths, 12 occurred in the ixabepilone group, and all were attributable to neutropenia. The protocol was subsequently amended to exclude patients with "grade 2 liver test abnormality in the presence of liver metastasis," Vahdat said. In all, 369 patients were randomized to the combination arm; 368 were assigned to Xeloda alone. "This was a patient population with quite a high disease burden. ...Most patients had more than two sites of disease, and 84 percent of patients had visceral metastasis. In addition, a quarter of the patients were ER, PR and HER-2 negative, the so-called triple negative phenotype," Vahdat noted. Most treatment-related adverse events were consistent with the safety profile of the individual agents, Bristol said. In addition, capecitabine-associated toxicities were not exacerbated by ixabepilone. The combination therapy did "cause neuropathy, as determined by a 23 percent grade 3-4 peripheral neuropathy rate versus zero for the control arm. ...[However] it was primarily sensory, it was cumulative and it was reversible, with a median time to resolution of six weeks," Vahdat said. The international open-label, Phase III trial enrolled 752 patients who had metastatic or locally advanced breast cancer and had either relapsed or their disease was refractory to anthracycline and taxane chemotherapies. The women were randomized to receive either ixabepilone in combination with capecitabine or capecitabine, the standard of care, alone. On the primary endpoint for the study, progression-free survival, the combination therapy "was significantly superior" at 5.8 months versus 4.2 months for capecitabine alone (p<0.0003), Vahdat reported. In addition, the response rate, a secondary endpoint, in the combination arm was "nearly two and a half times greater, at 35 percent, than that of the capecitabine arm, at 14 percent," she noted. Ixabepilone is a semisynthetic analog of epothilone B. Epothilones are a potential new class of antineoplastic, chemotherapy agents derived from a microorganism found in the mud of the Zambezi river. Bristol said it has begun enrollment in a study to identify biomarkers that can identify which patients will respond to epothilones as opposed to taxanes. Finding genetic markers will be helpful in understanding this new class of drugs and in identifying patients for which they might be the most appropriate therapy, Bristol said. The company has said that it plans to recapture its oncology presence by focusing on novel cytotoxic agents such as ixabepilone. The firm's near-term pipeline also includes vinflunine, in late-stage trials for non-small cell lung cancer and bladder cancer. - Shirley Haley ([email protected]) |