Results from a phase III randomized trial, presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO), show that weekly administration of either of two newer and significantly more costly agents, nanoparticle albumin bound (?nab?) paclitaxel (Abraxane?, Celgene Corporation) and ixabepilone (Ixempra?, Bristol-Myers Squibb), was not superior to standard weekly dosing of paclitaxel as first-line therapy for locally advanced or metastatic breast cancer. Furthermore, paclitaxel appears to offer better progression-free survival (PFS) than ixabepilone and fewer toxicities than nab-paclitaxel in this setting.

In practical terms, these findings suggest that many patients could do equally well on weekly paclitaxel with fewer side effects and at lower cost.

Similar or Superior Results?
?We wanted to know whether giving these newer microtubule agents when given on a weekly schedule would result in similar or superior effectiveness with improved toxicity profiles over the standard weekly paclitaxel regimen,? said lead study author Hope S. Rugo, MD, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. ?This study demonstrates that we should not simply assume that newer drugs are always better than the standard therapies. In metastatic breast cancer, we are constantly examining and refining dosing schedules, testing new therapies, and looking closely at molecular characteristics of patients? tumors to find the right treatment for the right patient, with the fewest toxicities.?

Study design
The study enrolled 799 patients who were randomized to receive one of the three therapies?paclitaxel, nab-paclitaxel or ixabepilone?on a weekly basis with each cycle consisting of three weeks of treatment followed by a one-week break The majority of patients enrolled in this trial received bevacizumab (Avastin?, Genentech), which became optional in March 2011.

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Median PFS was 10.6 months for those receiving paclitaxel, 9.2 months for nab-paclitaxel, and 7.6 months for ixabepilone. Weekly ixabepilone was significantly less effective than paclitaxel, and nab-paclitaxel was also not superior to paclitaxel. Grade 3 or 4 non-hematologic toxicities were also lowest in the paclitaxel arm, including sensory neuropathy (16% versus 25% for both experimental arms). Grade 3 or 4 hematologic toxicities were lowest in the ixabepilone arm, and highest in the nab-paclitaxel arm (12% versus 51%), compared to paclitaxel (21%). Coupled with the lack of superiority for the newer agents, this suggests that eligible patients can be appropriately treated with paclitaxel using a weekly schedule. Paclitaxel, nab-paclitaxel and ixabepilone are approved by the Food and Drug Administration for metastatic breast cancer.

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Which patients benefit?
The study also was designed to look at specific biologic features to understand which patients might benefit the most from one or another of the therapies, and which patients are more susceptible to peripheral neuropathy, a painful side effect of treatment. Investigators await the outcome of these correlative studies in the hopes of better defining which patients might do better on different agents or using different dosing schedules. The newer agents may offer lower toxicity or improved efficacy for some patients, based on molecular characteristics of tumors, but further studies looking at pre-determined patient subsets would be needed.

Stronger collaboration needed
?In this era of sophisticated research advances, these studies are a reminder of how we need to be thinking about every aspect of patent care, from managing costs and painful side effects to monitoring patients long after their treatment has ended,? said news briefing moderator Nicholas Vogelzang, MD Chair of ASCO?s Cancer Communications Committee and Chair and Medical Director, Developmental Therapeutics Committee, US Oncology, Comprehensive Cancer Centers of Nevada. ?As oncologists, we need to collaborate with our patients and colleagues across the medical field to put this evidence into practice.?

Presentation: Tuesday, June 5, 2012, 10:15 ? 10:30 AM CDT
Abstract: #CRA1002
Title: CALGB 40502/NCCTG N063H: Randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-paclitaxel (NP) or ixabepilone (Ix) with or without bevacizumab (B) as first-line therapy for locally recurrent or metastatic breast cancer (MBC).
Authors: Rugo HS, Barry WT, Moreno-Aspitia A, Lyss AP, Cirrincione C, Mayer EL, et al.
Photo credit: Chicago, IL – ASCO 2012 Annual Meeting: General Views at the American Society for Clinical Oncology (ASCO) Annual Meeting, Tuesday June 5, 2012. Over 31,000 physicians, researchers and healthcare professionals from over 100 countries are attending the meeting which is being held at the McCormick Convention center and features the latest cancer research in the areas of basic and clinical science. Photo by ? ASCO/Brian Powers 2012.

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