Christine Desmedt1, Marco Fornili2, Florian Clatot1,3, Romano Demicheli2, Davide De Bortoli2, Angelo Di Leo4, Giuseppe Viale5, Evandro de Azambuja6, John Crown7, Prudence A Francis8, Christos Sotiriou9, Martine Piccart10, Elia Biganzoli2. 1. Laboratory for Translational Breast Cancer Research, Department of Oncology, Leuven, Belgium. 2. Unit of Medical Statistics, Biometry and Bioinformatics Giulio A. Maccacaro Department of Clinical Sciences and Community Health & DSRC, University of Milan, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 3. Centre Henri Becquerel, Rouen, France. 4. Sandro Pitigliani Medical Oncology Unit, Hospital of Prato, Instituto Toscano Tumori, Prato, Italy. 5. European Institute of Oncology, University of Milan, Milan, Italy. 6. Breast European Adjuvant Study Team, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. 7. St Vincent's University Hospital, Dublin, Ireland. 8. Peter MacCallum Cancer Centre, St Vincent's Hospital, University of Melbourne, Australia; Breast Cancer Trials Australia and New Zealand, University of Newcastle, Australia. 9. Breast Cancer Translational Lab, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. 10. Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Abstract
PURPOSE: Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. Here, we reanalyzed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel-based chemotherapy in patients with breast cancer according to their baseline body mass index (BMI). PATIENTS AND METHODS: We retrospectively analyzed data from all of the patients in the adjuvant BIG 2-98 trial (ClinicalTrials.gov identifier: NCT00174655; N = 2,887) comparing non-docetaxel- to docetaxel-containing chemotherapy. BMI (kg/m2) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status. RESULTS: There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; P = .21) and 1.27 (95% CI, 1.01 to 1.60; P = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; P = .007) and 1.63 (95% CI, 1.27 to 2.09; P < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted P = .06) and OS (adjusted P = .04). CONCLUSION: This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition-based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.
PURPOSE: Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. Here, we reanalyzed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel-based chemotherapy in patients with breast cancer according to their baseline body mass index (BMI). PATIENTS AND METHODS: We retrospectively analyzed data from all of the patients in the adjuvant BIG 2-98 trial (ClinicalTrials.gov identifier: NCT00174655; N = 2,887) comparing non-docetaxel- to docetaxel-containing chemotherapy. BMI (kg/m2) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status. RESULTS: There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; P = .21) and 1.27 (95% CI, 1.01 to 1.60; P = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; P = .007) and 1.63 (95% CI, 1.27 to 2.09; P < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted P = .06) and OS (adjusted P = .04). CONCLUSION: This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition-based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.
Authors: Daniel L Hertz; Li Chen; N Lynn Henry; Jennifer J Griggs; Daniel F Hayes; Brian A Derstine; Grace L Su; Stewart C Wang; Manjunath P Pai Journal: Br J Clin Pharmacol Date: 2022-02-14 Impact factor: 3.716
Authors: Andrea Bellieni; Domenico Fusco; Alejandro Martin Sanchez; Gianluca Franceschini; Beatrice Di Capua; Elena Allocca; Enrico Di Stasio; Fabio Marazzi; Luca Tagliaferri; Riccardo Masetti; Roberto Bernabei; Giuseppe Ferdinando Colloca Journal: J Pers Med Date: 2021-03-26
Authors: Maret L Maliniak; Jasmine Miller-Kleinhenz; Deirdre P Cronin-Fenton; Timothy L Lash; Keerthi Gogineni; Emiel A M Janssen; Lauren E McCullough Journal: Cancers (Basel) Date: 2021-05-06 Impact factor: 6.639