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N Engl J Med. 2011 Oct 13;365(15):1396-405. doi: 10.1056/NEJMoa1105195. Epub 2011 Sep 25.

Breast-cancer adjuvant therapy with zoledronic acid.

Collaborators (260)

Schwarz M, White S, Kannourakis G, Underhill C, Chirgwin J, Della-Fiorentina S, Beale P, Koczwara B, Thomson J, Jennens R, Bell R, Della-Fiorentina S, Chirgwin J, Boyle F, Chipman M, White M, Francis P, Lewis C, Patterson K, Chern B, De Boer R, Baron-Hay S, Boyle F, Bayliss E, Beith J, White K, Snyder R, Abdi E, De Boer R, McDermott R, O'Reilly S, Keane M, Keane M, McCaffrey J, McCaffrey J, Bulger K, Gupta R, O'Reilly S, Kennedy J, Crown J, Coelho JL, Aramendia JM, Lluch A, Andrés R, Mayordomo JI, Catalán JG, Ciruelos EM, Gómez P, Vázquez F, Arnedos M, Gil JM, Brunet J, Colomer R, Chen ST, Cheng TW, Sunpaweravong P, Pataranutraporn P, Hutcheon AW, Todd R, Ahmed A, Moody AM, Wilson C, Crawford M, Irwin C, Stein R, Bridgewater C, Lee C, Ella W, Trask C, Fraser G, Ritchie D, McAleer JJ, Hardman PD, Wadd N, Bradley C, Price C, Chaturvedi A, Spensley S, Lowdell C, Owen R, Din O, Purohit, Armstrong A, Wardley A, Spooner D, O'Reilly S, Slater A, Sadler G, Dodwell D, Corder A, Lumsden G, Ritchie D, Hardman PD, Woodings P, Kelly S, Kumar S, Butt M, Mack P, Ramakrishnan S, Evans T, Kunkler, Ring A, Robinson A, Murray P, Canney P, Fraser G, Fraser J, Cawthorn S, Shere M, Fresco L, Reinecke L, Worlding J, Bishop J, Ellis P, Harries M, Dunn MG, Yosef H, Clark P, O'Reilly S, Dodwell D, Joseph J, Slater S, Joffe J, Hardman PD, Churn M, Sims E, Ahmed S, Chan S, Hornbuckle J, Khan S, Ellis P, Rigg A, Dodwell D, Murray E, Ah-See ML, Makris A, Barraclough L, Hunter R, Jain P, Jyothirmayi R, Fernando I, Stein R, Makris A, Churn M, Sumpter K, Verrill M, Dewar J, Thompson A, Harnett A, Napier M, Walls J, Newby J, Branson A, Macmillan C, Chan S, Hornbuckle J, McAdam K, Murray E, Kumar S, Roberts F, Mukherjee S, Rea D, Poole C, Ahmad A, Bowman A, Chakraborti P, Sims E, Whillis D, Hatton M, Wilson G, Barrett J, Bishop H, Winstanley J, Wheatley DA, Hong A, Jones A, Gaffney, Mohammed H, Jones R, Morgan C, Waters S, Hall V, Murray N, Raj S, O'Reilly S, Smith IE, Yarnold J, Agrawal R, Houston S, Bloomfield D, Allerton R, Copson E, Gregory K, Harvey M, Spooner D, Sreenivasan T, Upadhyay S, Venkitaraman R, Bertelli G, Leonard R, Stockdale A, Tsalic M, Bozzino JM, Mazdai G, Weber B, Simmonds P, Robinson A, Hyatt, Gallagher C, Assersohn L, Mansi J, Palmeri C, Perren T, Yuille F, Morgan, Patel A, Gendy R, Alcock C, Chatterjee S, Mallick U, Reinecke L, Rich A, Wright K, Patel A, Manifold I, Purohit K, Bailey N, Donnelly P, Goodman A, Whipp L, O'Hagan J, Schofield P, Rathmell AJ, Taylor W, Brunt AM, Hennessy C, Barrett-Lee P, Grieve RJ, Walji N, Jones DA, Grieve RJ, Moody AM, Cameron D, Green M, Bowman A, George D, Tomlinson MJ, Coleman R, Ashford R, Hall M, Cottrill C, Jones A, Hicks J, Mackay H, Lannigan A, Waterstone A, Bundred N, Mitra S, Dodwell D, Bishop J.

Author information

  • 1Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, United Kingdom. r.e.coleman@sheffield.ac.uk

Abstract

BACKGROUND:

Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients.

METHODS:

In this open-label phase 3 study, we randomly assigned 3360 patients to receive standard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed.

RESULTS:

At a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P=0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths--243 in the zoledronic acid group and 276 in the control group--were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P=0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P<0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups.

CONCLUSIONS:

These findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer. (Funded by Novartis Pharmaceuticals and the National Cancer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.).

Comment in

PMID:
21995387
[PubMed - indexed for MEDLINE]
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