Slamon et al trial results: TH very effective and equivalent to TCH in Stage IV her2+

[Lani]

Multicenter Phase III Randomized Trial Comparing Docetaxel and Trastuzumab With Docetaxel, Carboplatin, and Trastuzumab As First-Line Chemotherapy for Patients With HER2-Gene-Amplified Metastatic Breast Cancer (BCIRG 007 Study): Two Highly Active Therapeutic Regimens

1. Vicente Valero,
2. John Forbes,
3. Mark D. Pegram,
4. Tadeusz Pienkowski,
5. Wolfgang Eiermann,
6. Gunter von Minckwitz,
7. Henri Roche,
8. Miguel Martin,
9. John Crown,
10. John R. Mackey,
11. Pierre Fumoleau,
12. Janusz Rolski,
13. Zrinka Mrsic-Krmpotic,
14. Agnieszka Jagiello-Gruszfeld,
15. Alessandro Riva,
16. Marc Buyse,
17. Henry Taupin,
18. Guido Sauter,
19. Michael F. Press and
20. Dennis J. Slamon

+ Author Affiliations

1.
From The University of Texas M. D. Anderson Cancer Center, Houston, TX; Australia New Zealand Breast Cancer Trials Group, University of Newcastle, Calvary Mater Hospital, Newcastle, NSW, Australia; University of California, Los Angeles; University of Southern California, Los Angeles, CA; Marie Sklodowska-Curie Memorial Cancer Center, Warsaw and Krakow; Niepubliczny Zaklad Opieki Zdrowotnej Onko-Med, Olsztyn, Poland; Red Cross Women's Hospital, Munich; University Women's Hospital, Frankfurt, Germany; Institut Claudius Regaud, Toulouse; Cancer International Research Group, Paris; Centre Georges Francois Leclerc, Dijon, France; Hospital Gregorio Marañon and Grupo Español de Investigación en Cáncer de Mama, Madrid, Spain; St. Vincent's University Hospital, Irish Clinical Oncology Research Group, Dublin, Ireland; University of Alberta Cross Cancer Institute, Edmonton, Alberta, Canada; University Hospital for Tumors, Zagreb, Croatia; International Drug Development Institute, Louvain-la-Neuve; I-BioStat Center for Statistics, Hasselt University, Hasselt, Belgium; and Institute of Pathology, University of Basel, Basel, Switzerland.

1. Corresponding author: Vicente Valero, MD, Department of Breast Medical Oncology, Unit 1354, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: vvalero@mdanderson.org.

Abstract

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/m2) or TCH (trastuzumab plus carboplatin at area under the serum concentration-time curve 6 and docetaxel 75 mg/m2). 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/m2) and TCH (docetaxel, 75 mg/m2) demonstrated efficacy with acceptable toxicity in women with HER2-amplified MBC.
Footnotes

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Written on behalf of the Breast Cancer International Research Group BCIRG 007 trial investigators.
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Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Clinical trial information can be found for the following: NCT00047255.