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N Engl J Med. 2015 Feb 19;372(8):724-34. doi: 10.1056/NEJMoa1413513.

Pertuzumab, trastuzumab, and docetaxel in HER2-positive 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 S, 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 RG, 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

1
The authors' affiliations are listed in the Appendix.

Abstract

BACKGROUND:

In patients with metastatic breast cancer that is positive for human epidermal growth factor receptor 2 (HER2), progression-free survival was significantly improved after first-line therapy with pertuzumab, trastuzumab, and docetaxel, as compared with placebo, trastuzumab, and docetaxel. Overall survival was significantly improved with pertuzumab in an interim analysis without the median being reached. We report final prespecified overall survival results with a median follow-up of 50 months.

METHODS:

We randomly assigned patients with metastatic breast cancer who had not received previous chemotherapy or anti-HER2 therapy for their metastatic disease to receive the pertuzumab combination or the placebo combination. The secondary end points of overall survival, investigator-assessed progression-free survival, independently assessed duration of response, and safety are reported. Sensitivity analyses were adjusted for patients who crossed over from placebo to pertuzumab after the interim analysis.

RESULTS:

The median overall survival was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P<0.001), a difference of 15.7 months. This analysis was not adjusted for crossover to the pertuzumab group and is therefore conservative. Results of sensitivity analyses after adjustment for crossover were consistent. Median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (hazard ratio, 0.68; 95% CI, 0.58 to 0.80). Pertuzumab extended the median duration of response by 7.7 months, as independently assessed. Most adverse events occurred during the administration of docetaxel in the two groups, with long-term cardiac safety maintained.

CONCLUSIONS:

In patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel, as compared with the addition of placebo, significantly improved the median overall survival to 56.5 months and extended the results of previous analyses showing the efficacy of this drug combination. (Funded by F. Hoffmann-La Roche and Genentech; CLEOPATRA ClinicalTrials.gov number, NCT00567190.).

PMID:
25693012
PMCID:
PMC5584549
DOI:
10.1056/NEJMoa1413513
[Indexed for MEDLINE]
Free PMC Article

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