First-line treatment with cetuximab plus FOLFIRI, as compared with FOLFIRI alone, reduced the risk of progression of metastatic colorectal cancer. The benefit of cetuximab was limited to patients with KRAS wild-type tumors. (ClinicalTrials.gov number, NCT00154102.)

BACKGROUND Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab. METHODS We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety. RESULTS At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study. CONCLUSIONS The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk–benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.)

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Adjuvant chemotherapy with TAC, as compared with FAC, significantly improves the rates of disease-free and overall survival among women with operable node-positive breast cancer.

Background: Evaluation of the long-term benefit of biologically-based regimens of trastuzumab in the early breast cancer population, and optimization of trastuzumab integration to maximize efficacy and minimize cardiac toxicity.Material and Methods: We randomized HER2-positive (FISH+) breast cancer patients with axillary lymph node positive or high risk negative, to either standard AC (60/600 mg/m2 q3wk x4) followed by T (100 mg/m2 q3wk x 4) or two trastuzumab-containing regimens; AC followed by T with trastuzumab x 1 year or TCarbo (75 mg/m2/AUC6 q3wk x 6) with trastuzumab x 1 year. Patients were prospectively stratified by number of positive nodes (0, 1-3 vs 4+) and hormone receptor status. Patients with ER and/or PR positive (HR+) tumors received hormone-directed therapy for 5 yrs after chemotherapy. The primary endpoint was disease-free survival (DFS) with 80% power (0.05 significance level) to detect an absolute difference of 7%. Secondary endpoints include overall survival (OS) and safety, including cardiac toxicity (symptomatic events and asymptomatic LVEF decline). The first two protocol-specified analyses for this study were performed at 300 and 450 disease-related events. We now report the results of the third protocol-specified analysis conducted after 650 events, expected by end of June 2009.Results: A total of 3222 patients (1072 in AC-T, 1076 in AC-TH and 1074 in TCH) were recruited between April 2001 and March 2004. Baseline characteristics of the study population will be included. Cox analysis of DFS and OS (unadjusted and adjusted for nodal status) and cardiac toxicity data will be presented for the three treatment arms.Discussion: The results of this trial help define the role of trastuzumab in the breast cancer HER2-positive adjuvant setting, as well as the risks/benefits of adjuvant trastuzumab within the context of overall safety including cardiac toxicity. This latter objective is of particular importance given that many of these women may be cured of their disease in the adjuvant setting. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 62.

Crown for the 303 Study GroupPurpose: This phase III study compared docetaxel and doxorubicin in patients with metastatic breast cancer who had received previous alkylating agent-containing chemotherapy.Patients and Methods: Patients were randomized to receive an intravenous infusion of docetaxel 100 mg/m 2 or doxorubicin 75 mg/m 2 every 3 weeks for a maximum of seven treatment cycles.Results: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive docetaxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P ‫؍‬ .008). Docetaxel was also significantly more active than doxorubicin in patients with negative prognostic factors, such as visceral metastases (objective response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progression was longer in the docetaxel group (26 weeks v 21 weeks; difference not significant). Median overall survival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There was one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, febrile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhematologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, whereas diarrhea, neuropathy, fluid retention, and skin and nail changes were higher among patients receiving docetaxel.Conclusion: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer.

AT significantly improves TTP and ORR compared with AC in patients with MBC, but there is no difference in OS. AT represents a valid option for the treatment of MBC.

Addition of IV iron to darbepoetin alpha Q3W in patients with chemotherapy-induced anemia was well tolerated, resulting in an improved hematopoietic response rate and lower incidence of transfusions compared with darbepoetin alpha alone.