PURPOSE:Docetaxel-trastuzumab (TH) is effective therapy for HER2-amplified metastatic breast cancer (MBC). Preclinical findings of synergy between docetaxel, carboplatin, and trastuzumab (TCH) prompted a phase III randomized trial comparing TCH with TH in patients with HER2-amplified MBC. PATIENTS AND METHODS: Two hundred sixty-three patients were randomly assigned to receive eight 3-week cycles of TH (trastuzumab plus docetaxel 100 mg/m(2)) or TCH (trastuzumab plus carboplatin at area under the serum concentration-time curve 6 and docetaxel 75 mg/m(2)). Trastuzumab was given at 4 mg/kg loading dose followed by a 2 mg/kg dose once per week during chemotherapy, and then 6 mg/kg once every 3 weeks until progression. RESULTS: Patient characteristics were balanced between groups. There was no significant difference between TH and TCH in terms of the primary end point, time to progression (medians of 11.1 and 10.4 months, respectively; hazard ratio, 0.914; 95% CI, 0.694 to 1.203; P = .57), response rate (72% for both groups), or overall survival (medians of 37.1 and 37.4 months, respectively; P = .99). Rates of grades 3 or 4 adverse effects for TH and TCH, respectively, were neutropenic-related complications, 29% and 23%; thrombocytopenia, 2% and 15%; anemia, 5% and 11%; sensory neuropathy, 3% and 0.8%; fatigue, 5% and 12%; peripheral edema, 3.8% and 1.5%; and diarrhea, 2% and 10%. Two patients given TCH died of sepsis, and one patient given TH experienced sudden cardiac death. Absolute left ventricular ejection fraction decline > 15% was seen in 5.5% of patients on the TH arm and 6.7% of patients on the TCH arm. CONCLUSION: Adding carboplatin did not enhance TH antitumor activity.TH (docetaxel, 100 mg/m(2)) and TCH (docetaxel, 75 mg/m(2)) demonstrated efficacy with acceptable toxicity in women with HER2-amplified MBC.
RCT Entities:
PURPOSE:Docetaxel-trastuzumab (TH) is effective therapy for HER2-amplified metastatic breast cancer (MBC). Preclinical findings of synergy between docetaxel, carboplatin, and trastuzumab (TCH) prompted a phase III randomized trial comparing TCH with TH in patients with HER2-amplified MBC. PATIENTS AND METHODS: Two hundred sixty-three patients were randomly assigned to receive eight 3-week cycles of TH (trastuzumab plus docetaxel 100 mg/m(2)) or TCH (trastuzumab plus carboplatin at area under the serum concentration-time curve 6 and docetaxel 75 mg/m(2)). Trastuzumab was given at 4 mg/kg loading dose followed by a 2 mg/kg dose once per week during chemotherapy, and then 6 mg/kg once every 3 weeks until progression. RESULTS:Patient characteristics were balanced between groups. There was no significant difference between TH and TCH in terms of the primary end point, time to progression (medians of 11.1 and 10.4 months, respectively; hazard ratio, 0.914; 95% CI, 0.694 to 1.203; P = .57), response rate (72% for both groups), or overall survival (medians of 37.1 and 37.4 months, respectively; P = .99). Rates of grades 3 or 4 adverse effects for TH and TCH, respectively, were neutropenic-related complications, 29% and 23%; thrombocytopenia, 2% and 15%; anemia, 5% and 11%; sensory neuropathy, 3% and 0.8%; fatigue, 5% and 12%; peripheral edema, 3.8% and 1.5%; and diarrhea, 2% and 10%. Two patients given TCH died of sepsis, and one patient given TH experienced sudden cardiac death. Absolute left ventricular ejection fraction decline > 15% was seen in 5.5% of patients on the TH arm and 6.7% of patients on the TCH arm. CONCLUSION: Adding carboplatin did not enhance TH antitumor activity.TH (docetaxel, 100 mg/m(2)) and TCH (docetaxel, 75 mg/m(2)) demonstrated efficacy with acceptable toxicity in women with HER2-amplified MBC.
Authors: José Baselga; Javier Cortés; Sung-Bae Kim; Seock-Ah Im; Roberto Hegg; Young-Hyuck Im; Laslo Roman; José Luiz Pedrini; Tadeusz Pienkowski; Adam Knott; Emma Clark; Mark C Benyunes; Graham Ross; Sandra M Swain Journal: N Engl J Med Date: 2011-12-07 Impact factor: 91.245
Authors: Arti Hurria; Ilene S Browner; Harvey Jay Cohen; Crystal S Denlinger; Mollie deShazo; Martine Extermann; Apar Kishor P Ganti; Jimmie C Holland; Holly M Holmes; Mohana B Karlekar; Nancy L Keating; June McKoy; Bruno C Medeiros; Ewa Mrozek; Tracey O'Connor; Stephen H Petersdorf; Hope S Rugo; Rebecca A Silliman; William P Tew; Louise C Walter; Alva B Weir; Tanya Wildes Journal: J Natl Compr Canc Netw Date: 2012-02 Impact factor: 11.908
Authors: Gabrielle Rocque; Adedayo Onitilo; Jessica Engel; Erica Pettke; Alice Boshoven; Kyungmann Kim; Shailly Rishi; Bonnie Waack; Kari B Wisinski; Amye Tevaarwerk; Mark E Burkard Journal: Breast Cancer Res Treat Date: 2011-11-08 Impact factor: 4.872
Authors: Harold J Burstein; Martine J Piccart-Gebhart; Edith A Perez; Gabriel N Hortobagyi; Norman Wolmark; Kathy S Albain; Larry Norton; Eric P Winer; Clifford A Hudis Journal: J Clin Oncol Date: 2012-05-21 Impact factor: 44.544