Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.
Détails
ID Serval
serval:BIB_9D327ABC10CD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.
Périodique
Lancet Oncology
Collaborateur⸱rice⸱s
BIG 1-98 Collaborative Group, International Breast Cancer Study Group (IBCSG)
Contributeur⸱rice⸱s
Thürlimann B., Aebi S., Blacher L., Bonnefoi H., Coates A., Cufer T., Ejlertsen B., Forbes J., Gelber R., Giobbie-Hurder A., Goldhirsch A., Hiltbrunner A., Holmberg S., Maibach R., Martoni A., Mauriac L., MacGrogan G., Mouridsen H., Paridaens R., Phuong D., Price K., Rabaglio M., Rasmussen BB., Regan MM., Santoro A., Smith I., Wardley A., Viale G., Chaudri-Ross H., Segal S., Aebi S., Coates A., Colleoni M., Collins J., Cortés Funes H., Gelber R., Goldhirsch A., Green M., Hiltbrunner A., Holmberg S., Karlsson P., Kössler I., Láng I., Lindtner J., Paganetti F., de Stoppani M., Rudenstam C-., Senn H-., Stahel R., Thürlimann B., Veronesi A., Castiglione M., Hiltbrunner A., Rabaglio M., Egli G., Hawle H., Cliffe B., Ribeli-Hofmann S., Munarini F., Kammler R., Studer R., Ruepp B., Maibach R., Munarini N., Gelber R., Regan MM., Price K., Giobbie-Hurder A., Keshaviah A., Litman H., Cole BF., Sun Z., Gray PK., Huang H., Somos L., Timmers B., Nickerson L., Blacher L., Heckman Scolese T., Belisle M., Caporale M., Celano J., Dalfonso L., Dooley L., Fischer S., Galloway K., Gould J., Hinkle R., Holody M., Jones G., Krall R., Lippert S., Meshulam J., Mundy L., Pavlov-Shapiro A., Scott K., Scott M., Shepard S., Swick J., Uhteg L., Weinbaum D., Westby C., Zielinski T., Gusterson B., Mallon E., Viale G., Dell'Orto P., Mastropasqua M., Del Curto B., Waldie E., van Hoomissen I., De Smet M., Trostmann U., Schmidt W., Bolton A., Hackl W., Snyder R., Chirgwin J., Forbes J., Coates A., Boyle F., Lindsay D., Preece D., Cowell J., Talbot D., Whipp A., Abell F., Basser R., Bell R., Brady B., Blakey D., Briggs P., Burns I., Campbell P., Chao M., Chirgwin J., Chua B., Clarke K., Collins J., De Boer R., Din J., Doig R., Dowling A., Drummond R., Efe N., Fan S., Francis M., Francis P., Ganju V., Gibbs P., Goss G., Green M., Gregory P., Griffiths J., Haines I., Henderson M., Holmes R., James P., Kiffler J., Lehman M., Leyden M., Lim L., Lindeman G., Lynch R., Mann B., McKendrick J., McLachlan S., McLennan R., Mitchell G., Mitra S., Murphy C., Parker I., Phillips K., Porter I., Richardson G., Scarlet J., Sewak S., Shapiro J., Snyder R., Stanley R., Steer C., Stoney D., Strickland A., Toner G., Underhill C., White K., White M., Wirth A., Wong S., Holman Clinic WP. , Byram D., Byard I., Della-Fiorentina S., Goldrick A., Hovey E., Moylan E., Segelov E., Chan A., Buck M., Hastrich D., Ingram D., Van Hazel G., Willsher P., Wilcken N., Crombie C., Forbes J., Abell F., Ackland S., Bonaventura A., Cox S., Denham J., Gourlay R., Jackson D., Sillar R., Stewart J., Lewis C., Brigham B., Goldstein D., Friedlander M., Walpole E., Thompson D., Gill P., Bochner M., Coventry J., Kollias J., Malycha P., Olver I., Colosimo M., Cheuk R., Kenny L., McCarthy N., Wyld D., Young R., Harrup R., Kimber R., Lowenthal R., Trotter J., Bayliss E., Chan A., Ransom D., Byrne M., Buck M., Dewar J., Nowak A., Powell A., Van Hazel G., Abdi E., Brodribb R., Volobueva Z., Harnett P., Ahern V., Gurney H., Wilcken N., Harvey V., Evans B., Jones W., McCrystal M., Porter D., Thompson P., Vaughan M., Gibbs D., Atkinson C., Burcombe R., Fitzharris B., Hickey B., Jeffery M., Robinson B., McLaren B., Costello S., North J., Perez D., Campbell I., Gilbert L., Gannaway R., Jameson M., Kennedy I., Long J., Round G., Spellman L., Whittle D., Woolerton D., Menke C., Biazús J., Cericatto R., Cavalheiro J., Xavier N., Bittelbrunn A., Rabin E., Gutiérrez J., Arriagada R., Bronfman L., Zuñiga M., Gutiérrez J., Acevedo J., Torres S., León A., Salazar E., Soto Diaz L., Duval R., Oddeshede N., Venti M., Peña K., Puente L., Maidana V., Baeza R., Arriagada R., Olfos P., Solé J., Vinés E., Mariani C., Láng I., Hitre E., Szabó E., Horváth Z., Ganofszky E., Juhos E., Veronesi A., Crivellari D., Magri M., Buonadonna A., Coran F., Borsatti E., Candiani E., Massarut S., Roncadin M., Arcicasa M., Carbone A., Perin T., Gloghini A., Tondini C., Labianca R., Poletti P., Bettini A., Clerico M., Vincenti M., Malossi A., Seles E., Perfetti E., Sartorello B., Simoncini E., Marini G., Marpicati P., Farfaglia R., Bianchi A., Grigolato P., Lucini L., Frata P., Huscher A., Micheletti E., Fogazzi C., Medicina U., Artioli F., Cagossi K., Scaltriti L., Bandieri E., Botticelli L., Giovanardi G., Ravaioli A., Pasquini E., Rudnas B., Foghin L., Manzoni A., Visini M., Zavallone L., Ucci G., Colleoni M., Viale G., Veronesi P., Peruzzotti G., Corsetto L., Ghisini R., Renne G., Luini A., Orlando L., Torrisi R., Rocca A., De Pas T., Munzone E., Galimberti V., Zurrida S., Intra M., Nolé F., Orecchia R., Martinelli G., de Braud F., Goldhirsch A., Ravaioli A., Gianni L., Gome H., Cufer T., Pajk B., Cervek J., Werner I., Murray E., Govender D., Dalvie S., Erasmus T., Robertson B., Read B., Nel E., Toop J., Nedeva N., Panieri E., Vorobiof D., Chasen M., McMichael G., Mohammed C., Holmberg S., Holmberg S., Mattsson J., Sellström H., Lindberg B., Goldhirsch A., Herrmann R., Thürlimann B., Schönenberger A., Mingrone W., Honegger Ch., Bärtschi E., Neter M., Rederer M., Schär G., Rochlitz C., Herrmann R., Oertli D., Wight E., Moch H., Bernier J., Bronz L., Cavalli F., Gallerani E., Richetti A., Franzetti A., Conti-Beltraminelli M., Ghielmini M., Gyr T., Mauri S., Saletti P., Goldhirsch A., Pagani O., Graffeo R., Locatelli M., Longhi S., Rey PC., Ruggeri M., Zucca E., Wyss D., Mazzucchelli L., Pedrinis E., Rusca T., Aebi S., Fey M., Castiglione M., Rabaglio M., Aebi S., Fey M., Zuber M., Beck G., Aebi S., Fey M., Schönenberger R., Lüthi JM., Rauch D., Bonnefoi H., Egli F., Steiner R., Fehr P., Perey L., de Grandi P., Jeanneret W., Leyvraz S., Delaloye JF., Thürlimann B., Köberle D., Weisser F., Mattemann S., Müller A., Cerny T., Späti B., Höfliger M., Fürstenberger G., Bolliger B., Öhlschlegel C., Lorenz U., Bamert M., Kehl-Blank J., Vogel E., Thürlimann B., Hess D., Senn I., Köberle D., Ehrsam A., Nauer C., Öhlschlegel C., Kehl-Blank J., Vogel E., Widmer L., Häfner M., Pestalozzi B., Fehr M., Caduff R., Varga Z., Trüb R., Fink D., Bättig B., Buser K., Bürki N., Dieterle A., Hasler L., Mannhart-Harms M., Rageth C., Richner J., Spataro V., Umbricht M., Ellis P., Harris S., Akbar N., McVicars H., Lees C., Raman R., Crane G., Ejlertsen B., Mouridsen H., Mouridsen H., Jakobsen E., Cold S., Kamby C., Ewertz M., Vestlev PM., Andersen J., Grundtvig P., Sandberg E., Philip P., Madsen E., Moeller K., Haahr V., Johansson J., Mauriac L., Debled M., Bonnefoi H., Campo P., Larregain-Fournier D., Remy S., Auvray H., De Gislain C., Delille F., Porteret MC., Servent V., Chapoutier M., Tubiana-Mathieu N., Lavau-Denes S., Bosc P., Guastalla J., Bachelot T., Arbault C., Netter-Pinon G., Perrin V., Monnier A., Hammoud Y., Romieu G., Culine L., Pinosa V., Cany L., Maguire C., Daban A., Le Saux M., Grandon C., Kerbrat P., Catheline C., Veyret C., Jugieau E., Talon V., Le Mevel A., Maury S., Gladieff L., Lignon N., Dodwell D., Dodwell D., Joffe J., Drew P., Yorkshire W., Nejim A., Dodwell D., Horgan K., Lansdown M., Perren T., Coleman R., Campos D., Cóppola F., Martinez J., Freue M., Wainstein C., Zori Comba A., Cazap E., Roffo AH., Mickiewicz E., Mendez A., Balbiani L., Osuna A., Palazzo E., de Romedis M., Cagnolati S., Delfino C., Caccia G., de Angelis R., Fein L., Sala R., Nassurdi C., Berra A., Viroglio R., Blajman C., Requejo H., Silberman L., Birrell S., Eaton M., Hoffman C., Humeniuk V., Craft P., Stuart-Harris R., Yip D., Bell R., Abell F., Francis M., Kiffer J., Lynch R., McLennan R., White K., Green M., Basser R., Collins J., De Boer R., Din J., Efe N., Fan S., Lindeman G., Wong S., Green M., Basser R., Collins J., De Boer R., Din J., Efe N., Fan S., Lindeman G., Wong S., Stewart J., Abell F., Ackland S., Bonaventura A., Trotter J., Bayliss E., Chan A., Ransom D., Redfern A., de Souza P., Links M., Dalley D., Grygiel J., Ward R., Underhill C., Clarke K., Steer C., Walpole E., Thompson D., Nogaret J., Christiaens MR., Neven P., Paridaens R., Smeets A., Vergote I., Weltens C., Wildiers H., Focan C., Marcelis L., Etterbeek C., Kains J., Canon J-., André Vèsale C., Brohèe D., Gowing J., Yelle L., Dubé P., Vogel C., León Prieto M., Petrakova K., Palacova M., Demlova R., Siffnerova H., Fischer J., Bustova I., Kankova H., Pintova M., Vitek P., Abrahamova J., Kordikova D., Petruzelka L., Sedlackova E., Honova H., Heinrich B., Wischnik A., Oberhoff C., Schindler A., Münstedt K., Meyer D., Grosse R., Kölbl H., Schmidt W., Mink D., Jänicke F., Lück H., Dornoff W., Hoffmann G., Hackmann J., Bader W., Kahan Z., Pajkos G., Kristo K., Dank M., Nagykalnai T., Landherr L., Kner E., Kispál M., Dani£££Á£££ Á. , Martoni A., Zamagni C., Giaquinta S., Piana E., Mattioli R., Imperatori L., Santoro A., Carnaghi C., Rimassa L., Gasparini G., Sciarretta G., Morabito A., Barni S., Cazzaniga M., Cabiddu M., Puglisi F., Cellerino R., Antognoli S., Freddari F., Mantovani G., Massa E., Astara G., Segati R., Rosso R., Del Mastro L., Venturini M., Bighin C., Bajetta E., Zilembo N., Paleari D., Procopio G., Salvagni S., Perrone M., Franciosi V., Salvatore S., Catalano G., Luzi Fedeli S., Pinotti G., Giardina G., Vallini I., Massidda B., Ionta M., Deidda M., Nalli G., Sita G., Carreca I., Cucciarré S., Burgio D., Lombardo M., Pandoli G., Di Stefano P., Boni C., Bisagni G., Banzi M., Linarello P., Colosini G., Spasiano A., Caldonazzo A., Pacquola M., Sleeboom H., Rutten H., Luiten E., Roerdink HT., Roumen R., McLaren B., Costello S., North J., Perez D., Pfieffer M., Kennedy I., Campbell I., Gilbert L., Gannaway R., Jameson M., Long J., Round G., Spellman L., Whittle D., Woolerton D., Jassem J., Welnicka-Jaskiewicz M., Senkus-Konefka E., Matuszewska K., Koralewski P., Pernal J., Pienkowski T., Brewczynska E., Bauer-Kosinska B., Sienkiewicz-Kozlowska R., Jagiello-Gruszfeld A., Sudol K., Tujakowski J., Zurawski B., Pawlega J., Jablonska E., Zygulska A., Górnasiowa M., Filypczyk-Cisarz E., Pajak K., Damasceno M., Albano J., da Costa B., Costa L., Henriques A., Amaral H., Marques F., Komov D., Polikarpova S., Makhson A., Zabaznyi N., Vozny E., Dobrovolskaya N., Bolshakova S., Yurgina O., Emmanuel N., Korman D., Maslova I., Petrov NN., Semiglazov V., Ivanov V., Manikhas G., Dolmatov G., Apffelstaedt J., Eedes D., Slabber C., Coccia M., Maart K., Alés Martinez J., Aramburo P., Sánchez R., Rifa J., Martin J., Pérez-Carrión R., González Larriba J., Cubillo A., Jiménez M., Casado A., Fra J., Vieitez J., Esteban E., Lacave A., Wight E., Bartens S., Decio R., Güth U., Breitenstein U., Icli F., Dincol D., Baltali E., Ozisik Y., Topuz E., Basaran M., Aydiner A., Ozdedeli E., Harmancioglu O., Yilmaz A., Smith I., Thompson A., Wardley A., Hickish T., Neave F., Sabini G.
ISSN
1474-5488 (Electronic)
ISSN-L
1470-2045
Statut éditorial
Publié
Date de publication
2011
Volume
12
Numéro
12
Pages
1101-1108
Langue
anglais
Notes
Publication types: Clinical Trial, Phase III ; Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
BACKGROUND: Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up.
METHODS: BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years. Treatment has ended for all patients and detailed safety results for adverse events that occurred during the 5 years of treatment have been reported elsewhere. Follow-up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at clinicaltrials.govNCT00004205.
FINDINGS: 8010 patients were included in the trial, with a median follow-up of 8·1 years (range 0-12·4). 2459 were randomly assigned to monotherapy with tamoxifen for 5 years and 2463 to monotherapy with letrozole for 5 years. In the four-arm option of the trial, 1546 were randomly assigned to letrozole for 5 years, 1548 to tamoxifen for 5 years, 1540 to letrozole for 2 years followed by tamoxifen for 3 years, and 1548 to tamoxifen for 2 years followed by letrozole for 3 years. At a median follow-up of 8·7 years from randomisation (range 0-12·4), letrozole monotherapy was significantly better than tamoxifen, whether by IPCW or intention-to-treat analysis (IPCW disease-free survival HR 0·82 [95% CI 0·74-0·92], overall survival HR 0·79 [0·69-0·90], DRFI HR 0·79 [0·68-0·92], BCFI HR 0·80 [0·70-0·92]; intention-to-treat disease-free survival HR 0·86 [0·78-0·96], overall survival HR 0·87 [0·77-0·999], DRFI HR 0·86 [0·74-0·998], BCFI HR 0·86 [0·76-0·98]). At a median follow-up of 8·0 years from randomisation (range 0-11·2) for the comparison of the sequential groups with letrozole monotherapy, there were no statistically significant differences in any of the four endpoints for either sequence. 8-year intention-to-treat estimates (each with SE ≤1·1%) for letrozole monotherapy, letrozole followed by tamoxifen, and tamoxifen followed by letrozole were 78·6%, 77·8%, 77·3% for disease-free survival; 87·5%, 87·7%, 85·9% for overall survival; 89·9%, 88·7%, 88·1% for DRFI; and 86·1%, 85·3%, 84·3% for BCFI.
INTERPRETATION: For postmenopausal women with endocrine-responsive early breast cancer, a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared with tamoxifen montherapy. Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability.
FUNDING: Novartis, United States National Cancer Institute, International Breast Cancer Study Group.
METHODS: BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years. Treatment has ended for all patients and detailed safety results for adverse events that occurred during the 5 years of treatment have been reported elsewhere. Follow-up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at clinicaltrials.govNCT00004205.
FINDINGS: 8010 patients were included in the trial, with a median follow-up of 8·1 years (range 0-12·4). 2459 were randomly assigned to monotherapy with tamoxifen for 5 years and 2463 to monotherapy with letrozole for 5 years. In the four-arm option of the trial, 1546 were randomly assigned to letrozole for 5 years, 1548 to tamoxifen for 5 years, 1540 to letrozole for 2 years followed by tamoxifen for 3 years, and 1548 to tamoxifen for 2 years followed by letrozole for 3 years. At a median follow-up of 8·7 years from randomisation (range 0-12·4), letrozole monotherapy was significantly better than tamoxifen, whether by IPCW or intention-to-treat analysis (IPCW disease-free survival HR 0·82 [95% CI 0·74-0·92], overall survival HR 0·79 [0·69-0·90], DRFI HR 0·79 [0·68-0·92], BCFI HR 0·80 [0·70-0·92]; intention-to-treat disease-free survival HR 0·86 [0·78-0·96], overall survival HR 0·87 [0·77-0·999], DRFI HR 0·86 [0·74-0·998], BCFI HR 0·86 [0·76-0·98]). At a median follow-up of 8·0 years from randomisation (range 0-11·2) for the comparison of the sequential groups with letrozole monotherapy, there were no statistically significant differences in any of the four endpoints for either sequence. 8-year intention-to-treat estimates (each with SE ≤1·1%) for letrozole monotherapy, letrozole followed by tamoxifen, and tamoxifen followed by letrozole were 78·6%, 77·8%, 77·3% for disease-free survival; 87·5%, 87·7%, 85·9% for overall survival; 89·9%, 88·7%, 88·1% for DRFI; and 86·1%, 85·3%, 84·3% for BCFI.
INTERPRETATION: For postmenopausal women with endocrine-responsive early breast cancer, a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared with tamoxifen montherapy. Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability.
FUNDING: Novartis, United States National Cancer Institute, International Breast Cancer Study Group.
Mots-clé
Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Aromatase Inhibitors/administration & dosage, Australia, Breast Neoplasms/chemistry, Breast Neoplasms/drug therapy, Cross-Over Studies, Disease-Free Survival, Double-Blind Method, Europe, Female, Humans, Kaplan-Meier Estimate, Neoplasm Recurrence, Local, Neoplasms, Second Primary, New Zealand, Nitriles/administration & dosage, North America, Postmenopause, Proportional Hazards Models, Receptors, Steroid/analysis, Risk Factors, Selective Estrogen Receptor Modulators/administration & dosage, South Africa, South America, Tamoxifen/administration & dosage, Time Factors, Treatment Outcome, Triazoles/administration & dosage, Tumor Markers, Biological/analysis
Pubmed
Web of science
Création de la notice
07/02/2012 10:17
Dernière modification de la notice
20/08/2019 16:03
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