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N Engl J Med. 2012 Jan 12;366(2):109-19. doi: 10.1056/NEJMoa1113216. Epub 2011 Dec 7.

Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer.

Collaborators (211)

Bártoli MA, Bianconi MI, Kotliar M, Lacava JA, Matwiejuk M, Price PE, Varela M, Andrade J, Araujo R, Azevedo S, Cortes E, Costa e Silva E, Cubero D, Delgado G, Diz Mdel P, Eyll B, Franke F, Hegg R, Ismael G, Jendiroba D, Pedrini JL, Pereira R, Pinczowski H, Tokunaga P, Tosello C, Brezden-Masley C, Cheng Y, Ouyang X, Shen Z, Wang X, Wang L, Yau TK, Yeo W, Otero D, Soldic Z, Vrbanec D, Soria T, Kellokumpu-Lehtinen P, Pyrhönen S, Campone M, Coudert B, Ferrero JM, Priou F, Aktas B, Aulitzky W, Clemens M, Grischke EM, Hauschild M, Just M, Kirsch A, Kuemmel S, Maintz C, Marmé A, Mueller V, Schmidt M, Schneeweiss A, Schumacher C, Thomssen C, Wesenberg B, Castro-Salguero H, Hernandez Monroy C, Zelina-Toache LM, Amadori D, Angiolini C, Biganzoli L, Cinieri S, Gamucci T, Iacobelli S, Latini L, Montemurro F, Simoncini E, Aogi K, Fuji H, Horiguchi J, Inoue K, Ito Y, Iwata H, Kashiwaba M, Kohno N, Kuroi K, Masuda N, Nakagami K, Nakayama T, Nishimura R, Saji S, Sasaki Y, Sato N, Takeda K, Tokuda Y, Tsugawa K, Ueno T, Watanabe J, Yoshiaki R, Im SA, Im YH, Kim SB, Moon YW, Ro JS, Sohn JH, Grincuka E, Kudaba I, Purkalne G, Kostovska-Maneva L, Stefanovski P, Martinez G, Tellez G, Caguioa P, Chan V, Tudtud D, Foszczynska-Kloda M, Pienkowski T, Polkowski W, Starowsławska E, Tomczak P, Gorbunova V, Gotovkin E, Kiselev I, Kopp M, Lichinitser M, Merkulov V, Roman L, Semiglazov V, Shirinkin V, Lee SC, Wong ZW, Alba Conejo E, Baselga J, Batista N, Calvo L, Ciruelos E, Cortés J, Gil i Gil M, Gonzalez A, Hornedo Muguiro J, Morales S, Ribelles Entrena N, Sánchez Sde L, Sanchez Rovira P, Arpornwirat W, Dejthevaporn T, Maneechavakajorn J, Srimuninnimit V, Sriuranpong V, Sunpaweravong P, Ahmad R, Assersohn L, Boiangiu I, Davidson N, Gallagher C, Jones A, Miles D, O'Reilly S, Robinson A, Wheatley D, Agajanian R, Armor JF, Audeh MW, Behairy AS, Birhiray R, Blachly R, Blackwell K, Blanchard R, Blanchet P, Bowers BJ, Brufsky A, Budde L, Carroll RR, Charu V, Dakhil S, Daniel B, Ellerton JA, Fehrenbacher L, Flynn P, Franco S, Green N, Hansen V, Hargis J, Hendricks C, Hermann RC, Kallab A, Karwal M, Kato G, Kaufman P, Kennedy PS, Klein P, Lester EP, Lobo CF, Michaelson RA, Neidhart JA, Neidhart JD, Nguyen AD, O'Rourke T, Patel R, Patel T, Perez A, Quackenbush JA, Peterson CE, Polikoff JD, Prill SJ, Robles R, Rodriguez G, Senecal F, Sharma P, Smith R, Spicer D, Swain SA, Taguchi JA, Vogel CL, Waterhouse DM, Yadav S, Yardley DA.

Author information

  • 1Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA. jbaselga@partners.org

Abstract

BACKGROUND:

The anti-human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody trastuzumab improves the outcome in patients with HER2-positive metastatic breast cancer. However, most cases of advanced disease eventually progress. Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of trastuzumab, and combination therapy with the two antibodies has shown promising activity and an acceptable safety profile in phase 2 studies involving patients with HER2-positive breast cancer.

METHODS:

We randomly assigned 808 patients with HER2-positive metastatic breast cancer to receive placebo plus trastuzumab plus docetaxel (control group) or pertuzumab plus trastuzumab plus docetaxel (pertuzumab group) as first-line treatment until the time of disease progression or the development of toxic effects that could not be effectively managed. The primary end point was independently assessed progression-free survival. Secondary end points included overall survival, progression-free survival as assessed by the investigator, the objective response rate, and safety.

RESULTS:

The median progression-free survival was 12.4 months in the control group, as compared with 18.5 months in the pertuzumab group (hazard ratio for progression or death, 0.62; 95% confidence interval, 0.51 to 0.75; P<0.001). The interim analysis of overall survival showed a strong trend in favor of pertuzumab plus trastuzumab plus docetaxel. The safety profile was generally similar in the two groups, with no increase in left ventricular systolic dysfunction; the rates of febrile neutropenia and diarrhea of grade 3 or above were higher in the pertuzumab group than in the control group.

CONCLUSIONS:

The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT00567190.).

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PMID:
22149875
[PubMed - indexed for MEDLINE]
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