Metastatic Breast Cancer (2004)

NEW ORLEANS—A novel albumin-bound version of paclitaxel shows superior anti-tumor activity and less toxicity compared with standard paclitaxel for the treatment of metastatic breast cancer, according to a report here at the ASCO Annual Meeting. The drug, ABI-007 (Abraxane) is a nanoparticle albumin-bound paclitaxel that is one-hundredth the size of a single red blood cell. The albumin binds to a protein that may facilitate absorption and transport of hydrophobic molecules to tumor cells, explained Joanne Blum, MD, PhD, Director of the Breast Cancer Risk Evaluation Program at Texas Oncology in Dallas. ABI-007 differentiates itself from other taxanes because “it enables us to administer more cancer-fighting paclitaxel to the patient without the increase in side effects one might expect to see with currently available taxane therapies,” said Dr. Blum, who also is associated with the Charles A. Sammons Cancer Center at Baylor University Medical Center. “It appears that Abraxane allows for more cancer-fighting drug to be given to a patient, more of that drug to actually reach the tumor site in the body, and more of the drug to get inside of the tumor to fight cancer cells,” she said.Figure: Joanne Blum, MD, PhD: “It appears that Abraxane allows for more cancer-fighting drug to be given to a patient, more of that drug to actually reach the tumor site in the body, and more of the drug to get inside of the tumor to fight cancer cells.”In a previous randomized, Phase III trial of 454 patients with metastatic breast cancer, ABI-007 administered at 260 mg/m2 intravenously for 30 minutes weekly for three weeks demonstrated a superior response rate (33%) in a head-to-head comparison to standard therapy with paclitaxel (19%). Dr. Blum conducted a Phase II study of ABI-007 administered at 100 mg/m2 IV weekly for three weeks followed by one week of rest in 106 metastatic breast cancer patients whose disease had previously progressed on paclitaxel or docetaxel or had relapsed within 12 months of adjuvant taxane therapy. ABI-007 was administered without steroid/antihistamine premedication or prophylaxis with granulocyte colony-stimulating factor. Most of the patients, whose average age was 54, had a poor prognosis—91% had visceral disease, two thirds had more than three metastatic sites, and 89% had tumor growth while on taxanes. The overall response rate to ABI-007 was 15%, with disease controlled in 30% of patients at six months, Dr. Blum reported. More than one third (38%) of patients had a projected progression-free survival of four months, and the projected 12-month survival rate was 38%, with a median survival time of nine months. Several patients continued to receive the drug weekly for more than a year, and one patient approached two years on the drug, Dr. Blum said. Very Well Tolerated The drug was extremely well-tolerated, she added. “There was minimal severe toxicity—only 1% Grade 4 neutropenia, no Grade 4 nonhematologic toxicity, no severe hypersensitivity reactions, and only 4% Grade 3 sensory neuropathy.” The safety profile compares favorably to that reported using standard weekly paclitaxel at 80 mg/m2 in terms of Grade 4 neutropenia (5%) and Grade 3 neuropathy (9%). She noted that almost all (91%) of the patients in her study were treated at full dose with no dose reductions. Edith Perez, MD, Director of the Breast Cancer Program at the Mayo Clinic in Jacksonville, FL, commented that neurotoxicity is a modest problem with taxanes, depending on the dose-schedule. “Abraxane looks especially great when it is used weekly. It has a better tolerability profile than the available taxanes,” she said. Continuing Studies In light of the very low incidence of Grade 3 or 4 toxicities, further studies of ABI-007 are focusing on neoadjuvant and adjuvant breast cancer, higher weekly doses (125 mg/m2), and combinations with other drugs, Dr. Blum said. “Abraxane will be studied as doublets and triplets with capecitabine and carboplatin in earlier stage patients.” Taking together the novel mechanism of action and the clinical experience, “Abraxane, administered either weekly or once a week for three weeks, offers an important, exciting new treatment option for advanced breast cancer.” ‘More User-Friendly’ Also asked for a comment, William Gradishar, MD, Associate Professor of Medicine in the Division of Hematology and Medical Oncology/ Department of Medicine at Northwestern University Medical School, said, “I think the upside to the data is the drug's activity in patients who already had received taxanes and progressed. Seeing any response is fairly remarkable.” Dr. Gradishar said he believes that ABI-007 “might be a more user-friendly drug. In clinical practice, we use weekly Taxol therapy, and over time, run into neuropathy. The neuropathy with weekly Abraxane was half what we would expect using Taxol.”