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N Engl J Med. 2017 Jul 13;377(2):122-131. doi: 10.1056/NEJMoa1703643. Epub 2017 Jun 5.

Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.

Collaborators (584)

Kirk S, Eng-Wong J, Gnant M, Möbus V, Wilcken N, Tjan-Heynen V, Jassem J, Andersson M, Cardoso F, Bonnefoi H, Fein L, Jackisch C, Gomez Moreno H, Lescure AR, Torres Ulloa MR, Tomasello G, Jerusalem G, Walshe J, Bliss J, Dent S, Cameron D, de la Pena L, Janni W, Bergh J, Liu TW, Nitz U, Winer E, Hudis C, Toi M, Twelves C, Ah Im S, Kaufman B, Pienkowski T, Reaby L, Frank E, Krop I, Loi S, Kiermaier A, Henot F, van Dooren V, Guillaume S, Ponde N, McFadden E, McConnell R, Daly F, Wermuth P, Bonierbale E, Thomssen C, Ewer M, Plummer C, Krop I, Kiermaier A, Loi S, Bradbury I, Phillips G, Hasmann M, Amler L, André F, Frank E, Gralow JR, Antman KH, Bogaerts J, Muggia FM, Sawyer DB, Steger G, Greil R, Singer C, Petzer A, Sevelda P, Marth C, Stoeger H, Haslbauer F, Thaler J, Lang A, Weiss H, Lueck HJ, Untch M, Moebus V, Mueller V, Schmidt M, Schmatloch S, Lehnert A, Kuehn T, Solomayer E, Liedtke C, Wilcken N, Khasraw M, Boyle F, Lombard J, Selva S, Kee DD, McCarthy N, Woodward N, Harris M, Francis P, Boadle D, Dewar J, Boyce A, Isaacs R, Kuper M, Bos M, Honkoop A, Vrijaldenhoven S, Ten T, Tjan-Heijnen V, Bernstein V, Salim M, Dent S, Bordeleau L, Topic D, Elser C, Findlay B, Lohrisch C, Grenier D, Sawhney R, Pritchard K, Rayson D, Roy JA, Joy A, Vandenberg T, Zibdawi L, Desbiens C, Sideris L, Bedard P, Myers R, Webster M, Mates M, Young S, Jassem J, Jinga DC, Grecea D, Andersson M, Jakobsen EH, Harder Brix E, Tuxen G, Cold S, Luczak A, Glavicic V, Borms M, Henry S, Wildiers H, Altintas S, Drumea K, Zarba J, Marschner NW, Kunz G, Hauzenberger T, Klare P, Graffunder G, Just M, Rezai M, Solbach C, Tio J, Hanusch C, Jackisch C, Nusch A, Bauer W, Hackmann J, Weniger J, Wachsmann GT, Vesper A, Tome O, Krabisch P, Langanke D, Scherpe A, Gerber B, Luebbe K, Mundhenke C, Doering G, Kohls A, Hocke A, Belau A, Ettl J, Lorenz R, Schlag R, Mahlberg R, Decker T, Groh U, Schneeweiss A, Gomez H, Alba Conejo E, Lopez Vega JM, Alvarez Lopez I, Antolin Novoa S, Anton Torres A, Barnadas Molins A, Batista Lopez N, Bayo Calero JL, Chacón López-Muñiz I, de la Haba Rodriguez J, Garcia-Saenz JA, Martin Jimenez M, Margeli M, Martinez Janez N, Munoz Mateu M, Plazaola Alcibar A, Ramos Vazquez M, Rodriguez Sanchez C, Rodriguez Lescure A, Ruiz Simo A, Ruiz Borrego M, Rodriguez M, Lomas Garrido M, Santaballa Bertran A, Fernandez Morales L, Servitja S, Pernas Simon S, Garcia Garre E, Gonzalez Martin A, Calvo I, Martinez de Duenas E, Gallardo EJ, Salman P, Mattioli R, Ardizzoia A, Roila F, Cagossi K, Mosconi A, Verusio C, Ballestrero A, Bonetti A, Bisagni G, Graiff C, Jerusalem G, Láng I, Cinieri S, Puglisi F, Colleoni M, Simoncini E, di Lauro V, Biganzoli L, Bernardo A, Torrisi R, Gennari A, Eniu A, Borstnar S, Klint L, Rochlitz C, Ruhstaller T, Tausch C, Aebi S, Bodmer A, Walshe J, Coate L, Hennessy B, Kennedy MJ, O’Reilly S, Keane M, Kelly C, Wheatley D, Archer C, Adams J, Brunt A, Cameron D, Churn M, Winter M, Hogg M, Stephens P, Jenkins P, Levitt N, McAdam K, Miles D, Mukesh M, O’Reilly S, Parton M, Poole C, Conibear J, Sherwin E, Stein R, Perren T, Wardley A, Barrett-Lee P, Khan S, Perello Martorell B, Ciruelos E, Codes de Villena M, Lluch Hernandez A, Lopez Lopez R, Morales S, Caranana Ballerini V, Saura Manich C, Garau Llinas I, Overkamp F, Tesch H, Rack B, Grischke EM, Beck T, Kast K, Bauerfeind I, Fasching P, Wagner H, Fornander T, Dabrosin C, Bengtsson NO, Lindman H, Huang CS, Tseng LM, Kuo YL, Hou MF, Yu JC, Yang Y, Bonnefoi H, Bachelot T, Dieras V, Saghatchian-D’Assign M, Extra JM, Mouret Reynier MA, Dalenc F, Romieu G, Coudert B, Campone M, Brain E, Tennevet Bouilly I, de la Motte Rouge T, Ferrero JM, Simon H, Jacquin JP, Garnier-Tixidre C, Barthelemy P, Tubiana-Mathieu N, Raban N, Priou F, Hardy-Bessard AC, Dohollou N, Levache CB, Despax R, Legouffe E, Grenier J, Servent Hanon V, Coeffic D, Jouannaud C, Soulie P, Spaeth D, Uwer L, Piot G, Noesselt T, Von Schumann R, Koehne CH, Augustin D, Kramer S, Uleer C Jun, Schumacher C, Canon JL, Dirix L, Mebis J, Popov V, Kurteva G, Dudov A, Shen K, Shen P, Wang C, Liu J, Ouyang X, Ma B, Sheng Y, Wu B, Xu B, Shao Z, Jiang Z, Liao N, Huang T, Geng C, Pang D, Zhang Q, Roujun P, Li Q, Yu S, Cheng Y, Li W, Ouyang Q, Gonzalez M, Segova J, Saldarriaga N, Bruges Maya R, Podolski P, Vrdoljak E, Vojnovic Z, Melichar B, Petrakova K, Kubala E, Vanasek J, Rosales O, Finlander SJ, Achille M, Gozy M, Pottier V, Prevost J, Castro H, Kwong A, Chiu J, Pajkos G, Pintér T, Horvath Z, Kahán Z, Papai Z, Piko B, Ben-Baruch N, Kaufman B, Ryvo L, Yerushalmi R, Zamagni C, de Laurentiis M, Tassone P, Montemurro F, de Placido S, Ruggeri E, del Mastro L, Colantuoni G, Bajetta E, Ishida K, Sato N, Fujita T, Horiguchi J, Saeki T, Inoue K, Mukai H, Miyaki T, Fujiwara Y, Kuroi K, Ito Y, Ishikawa T, Tsugawa K, Tokuda Y, Watanabe J, Nakagami K, Iwata H, Suzuki E, Masuda N, Ohtani S, Aogi K, Tukunaga E, Rai Y, Nakayama T, Nishimura R, Im SA, Young R, Park KH, Joo HS, Kim JH, Kim SY, Lopez Lopez F, Hernandez C, Sanchez Llamas B, Martinez G, Cardona Huerta S, Gonzalez J, Gonzalez Trujillo JL, Lazaro Leon JM, Rosales Saracco L, Dominguez A, Morales Espinosa P, Lopez R, Alcedo JC, Zorrilla J, Figueroa A, Alarcon E, Caguioa P, Pua PF, Fuerte F, Chmielowska E, Radecka B, Nowecki Z, Wojtukiewicz M, Chudzik M, Volovat C, Kostalanova Y, Vladimirov V, Mikhaylyukova N, Tuaeva E, Kuzmin A, Gorbunova V, Demetriou G, Dreosti L, Sherriff A, Chen ST, Pornpraserthsuk P, Tharavichitkul E, Luechakiettisak P, Samphao S, Chenbhanich U, Bondarenko I, Shparyk Y, Paramonov V, Ponomarova O, Galaychuk I, Sinielnikov I, Kostinskyy I, Fehrenbacher L, Polikoff J, Johnson P, Kathleen K, Sparano J, le Linsqwister N, Mazurczak M, Caskey J, Moreno Aspitia A, Gross H, Mowat R, Hirsch RA, Dakhil S, Jurgens D, Onitilo A, Shao R, Raymond M, Morginstin M, Orlowski R, Iannotti N, Cunningham J, Brufsky A, Eisenberg P, Patel T, Isaacs C, Benjamin S, Bubis J, Shumaker G, Panelli V, Bordoni R, Anderson D, Wang X, Weisberg T, Hansen V, Mita M, Kingsley C, Boles S, Ma C, Rohatgi N, Kim K, Riseberg D, Hendricks C, Oyola R, Isakoff S, Klein P, Nagpal S, Lyss A, Soori G, Kozloff M, Brown A, Bulgaru A, Kaufman P, Salkeni M, Kato G, Holladay C, Hantel A, Sinclair S, Gallagher C, Dang C, DeMichele A, Zimbler H, Jaslowski A, Ali MA, Hahn O, Mayer I, Raza A, Jani C, Rao R, Albain K, Isaacs C, Levine E, Goble S, Weaver RW, Hart L, Daniel B, Karwal M, Young R, Hutchinson A, Carey L, Blanchard R, Ward P, Paul D, Keogh G, McIntyre K, Richards D, Savin M, Stokoe C, Zweibach A, Tedesco K, Balaraman R, Gupta M, Rivera R, Holmes F, Smith J, Oommen S, Osborne C, Edenfield W.

Abstract

BACKGROUND:

Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer.

METHODS:

We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8% with pertuzumab and 89.2% with placebo.

RESULTS:

In the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor-negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P=0.045). The estimates of the 3-year rates of invasive-disease-free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease-free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease-free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P=0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%).

CONCLUSIONS:

Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo. (Funded by F. Hoffmann-La Roche/Genentech; APHINITY ClinicalTrials.gov number, NCT01358877 .).

Comment in

PMID:
28581356
PMCID:
PMC5538020
DOI:
10.1056/NEJMoa1703643
[Indexed for MEDLINE]
Free PMC Article

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