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Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials

2023; Elsevier BV; Volume: 401; Issue: 10384 Linguagem: Inglês

10.1016/s0140-6736(23)00285-4

1474-547X

Jeremy Braybrooke, Rosie Bradley, Richard Gray, Robert K. Hills, Hongchao Pan, Richárd Pető, David Dodwell, Paul McGale, Carolyn Taylor, Tomohiko Aihara, Stewart Anderson, Joanne L. Blum, Fátima Cardoso, Xiaosong Chen, John Crown, Bent Ejlertsen, Thomas W. P. Friedl, Nadia Harbeck, Wolfgang Janni, Maj‐Britt Jensen, E. Mamounas, Kazutaka Narui, Ulrike Nitz, Larry Norton, Joyce O’Shaughnessy, Martine Piccart, Nicholas J. Robert, Zhi‐Ming Shao, Dennis Slamon, Joseph A. Sparano, Toru Watanabe, Greg Yothers, Ke‐Da Yu, Richard Berry, Clare Boddington, Mike Clarke, Christina Davies, Lucy Davies, Fran Duane, Vaughan Evans, Jo Gay, Lucy Gettins, Jon Godwin, Sam James, Hui Lui, Zulian Lui, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Simon Read, Ewan Straiton, Aman U. Buzdar, Vera J. Suman, Kelly K. Hunt, Robert Leonard, Janine Mansi, Catherine Delbaldo, Pascal Piedbois, Emmanuel Quinaux, Christian Fesl, Michael Gnant, Lidija Sölkner, Guenther G. Steger, Hans Petter Eikesdal, Per Eystein Lønning, Valerie Bée, Helena Fung, John R. Mackey, Miguel Martín, Michael F. Press, Evandro de Azambuja, Richard D. Gelber, Meredith M. Regan, Angelo Di Leo, Veerle Van Dooren, J.-M. Nogaret, John M.S. Bartlett, Bingshu E. Chen, Karen A. Gelmon, Paul E. Goss, Mark N. Levine, Wendy R. Parulekar, Kathleen I. Pritchard, Lois E. Shepherd, Donald A. Berry, Constance Cirrincione, Lawrence N. Shulman, Eric P. Winer, Rebecca Gelman, Jay R. Harris, Craig Henderson, Charles L. Shapiro, Peer Christiansen, Marianne Ewertz, Henning T. Mouridsen, Elise Van Leeuwen, Sabine C. Linn, Annelot G.J. van Rossum, Harm van Tinteren, Erik van Werkhoven, Lori J. Goldstein, Robert P. Gray, W. Eiermann, Luca Gianni, Pinuccia Valagussa, Jan Bogaerts, Hervé Bonnefoi, Coralie Poncet, Riikka Huovinen, Heikki Joensuu, Jacques Bonneterre, P. Fargeot, P. Fumoleau, Pierre Kerbrat, Élisabeth Luporsi, Moïse Namer, Eva Carrasco, Miguel Ángel Seguí, Christoph Meisner, Sibylle Loibl, Valentina Nekljudova, Christoph Thomssen, Gϋnter von Minckwitz, Sherko Kümmel, Massimo Lopez, Patrizia Vici, George Fountzilas, Georgia-Angeliki Koliou, Dimitriοs Mavroudis, Emmanouil Saloustros, Étienne Brain, Suzette Delaloge, Stefan Michiels, Simone Mathoulin‐Pélissier, José Bines, Roberta Sarmento, Gianni Bonadonna, Cristina Brambilla, Anna Rossi, Judith M. Bliss, R. Charles Coombes, Lucy Kilburn, M. Marty, Dino Amadori, Francesco Boccardo, Oriana Nanni, A. Rubagotti, Emanuela Scarpi, Norikazu Masuda, Masakazu Toi, Takayuki Ueno, Takashi Ishikawa, Koji Matsumoto, Shintaro Takao, Harald Sommer, Pericles Foroglou, G. Giokas, D. Kondylis, B Lissaios, Mattea Reinisch, Keun Seok Lee, Byung‐Ho Nam, Jung Sil Ro, A. De Matteis, Federica Perrone, Gong Tang, Norman Wolmark, Yasuo Hozumi, Yasuo Nomura, Helena Earl, Louise Hiller, Anne-Laure Vallier, Lucia De Mastro, M. Venturini, T. Delozier, Jérôme Lemonnier, Anne‐Laure Martin, Henri Roché, M. Spielmann, Xiasong Chen, Kunwei Shen, Kathy S. Albain, William E. Barlow, G. Thomas Budd, Julie R. Gralow, Daniel Hayes, Peter Bartlett-Lee, Peter Ellis, Angelo Raffaele Bianco, Michelino De Laurentiis, Sabino De Placido, Hans Wildiers, Limin Hsu, Oleg Eremin, Leslie G. Walker, Johan Ahlgren, Carl Blomqvist, Lars Holmberg, Henrik Lindman, Lina Asmar, Stephen E. Jones, Oleg Gluz, Cornelia Liedtke, R. Arriagada, Elizabeth Bergsten-Nordström, Lisa A. Carey, Robert E. Coleman, Jack Cuzick, Nancy E. Davidson, James J. Dignam, Mitch Dowsett, Prudence A. Francis, Matthew P. Goetz, Pam Goodwin, Pat Halpin-Murphy, Catherine Hill, Reshma Jagsi, Hirofumi Mukai, Yasuo Ohashi, Lori J. Pierce, Philip Poortmans, Vinod Raina, Daniel Rea, J.F.R. Robertson, Emiel J. Rutgers, Roberto Salgado, Tanja Španič, Andrew Tutt, Giuseppe Viale, Xiang Wang, Timothy J. Whelan, Nicholas Wilcken, David Cameron, Jonas Bergh, Sandra M. Swain,

HER2/EGFR in Cancer Research

Summary Background Anthracycline–taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline, and the comparative benefits of different anthracycline–taxane regimens. Methods We did an individual patient-level meta-analysis of randomised trials comparing taxane regimens with versus without anthracycline, and updated our previous meta-analysis of anthracycline regimens with versus without taxane, as well as analysing 44 trials in six related comparisons. We searched databases, including MEDLINE, Embase, the Cochrane Library, and meeting abstracts to identify trials assessing anthracycline and taxane chemotherapy. Adjuvant or neoadjuvant trials were eligible if they began before Jan 1, 2012. Primary outcomes were breast cancer recurrence and cause-specific mortality. Log-rank analyses yielded first-event rate ratios (RRs) and CIs. Findings 28 trials of taxane regimens with or without anthracycline were identified, of which 23 were deemed eligible, and 15 provided data on 18 103 women. Across all 15 trials that provided individual data, recurrence rates were 14% lower on average (RR 0·86, 95% CI 0·79–0·93; p=0·0004) with taxane regimens including anthracycline than those without. Non-breast cancer deaths were not increased but there was one additional acute myeloid leukaemia case per 700 women treated. The clearest reductions in recurrence were found when anthracycline was added concurrently to docetaxel plus cyclophosphamide versus the same dose of docetaxel plus cyclophosphamide (10-year recurrence risk 12·3% vs 21·0%; risk difference 8·7%, 95% CI 4·5–12·9; RR 0·58, 0·47–0·73; p<0·0001). 10-year breast cancer mortality in this group was reduced by 4·2% (0·4–8·1; p=0·0034). No significant reduction in recurrence risk was found for sequential schedules of taxane plus anthracycline when compared with docetaxel plus cyclophosphamide (RR 0·94, 0·83–1·06; p=0·30). For the analysis of anthracycline regimens with versus without taxane, 35 trials (n=52 976) provided individual patient data. Larger recurrence reductions were seen from adding taxane to anthracycline regimens when the cumulative dose of anthracycline was the same in each group (RR 0·87, 0·82–0·93; p<0·0001; n=11 167) than in trials with two-fold higher cumulative doses of non-taxane (mostly anthracycline) in the control group than in the taxane group (RR 0·96, 0·90–1·03; p=0·27; n=14 620). Direct comparisons between anthracycline and taxane regimens showed that a higher cumulative dose and more dose-intense schedules were more efficacious. The proportional reductions in recurrence for taxane plus anthracycline were similar in oestrogen receptor-positive and oestrogen receptor-negative disease, and did not differ by age, nodal status, or tumour size or grade. Interpretation Anthracycline plus taxane regimens are most efficacious at reducing breast cancer recurrence and death. Regimens with higher cumulative doses of anthracycline plus taxane provide the greatest benefits, challenging the current trend in clinical practice and guidelines towards non-anthracycline chemotherapy, particularly shorter regimens, such as four cycles of docetaxel–cyclophosphamide. By bringing together data from almost all relevant trials, this meta-analysis provides a reliable evidence base to inform individual treatment decisions, clinical guidelines, and the design of future clinical trials. Funding Cancer Research UK, UK Medical Research Council.