Panther: A Study Comparing Biweekly and Tailored EC-T Versus Three Weekly FEC-T in Breast Cancer Patients

Summary

This is an adjuvant, open, prospective, randomized study to compare: A. Individually tailored and two weekly dosed epirubicin + cyclophosphamide followed by a three weeks break followed by biweekly and tailored docetaxel (dtEC→dtT) given every second week, to B. Fixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel (FEC→T). Patients with primary node-positive or high risk lymph node negative breast cancer will be eligible for the study. The primary objective of the phase 3 study is to compare breast cancer relapse-free survival (BCRFS) between the dtEC→dtT and FE100C→T. To detect a five-year BCRFS difference of 0.710 to 0.790 about 1000 patients per arm will be needed. They will be recruited during four years and followed another two years for breast cancer events. Secondary objectives are to compare 1. Distant disease-free survival (DDFS) 2. Event-free survival and 3. Overall survival 4. Health-related quality of life and toxicity analyses according to CTC 5. Outcome in relation to tumour biological factors and polymorphism patterns 1. RFS in relation to the Sorlie classes using immunohistochemical markers and/or gene expression profiling comparing A vs B arm 2. RFS with receptor positive disease (analyzed in the local laboratories as described in the CRFs and also analyzed as continuous variables) in the comparison between the A- and B- arms. 3. RFS with high and low proliferation, respectively, (analyzed in the local laboratories as described in the CRFs and also analyzed as a continuous variable, or centrally analyzed), in the comparison between the A- and B-arms. 4. RFS in relation to HER-2/neu status (analyzed in the local laboratories as described in the CRFs) in the primary cancers in the comparison between the A- and B-arms and analyzed whether trastuzumab was given in sequence or concurrently. 5. RFS analyzed in relation to other molecular markers (e.g. gene expression profiling/ sequencing) in the primary cancers and SNPs signatures in normal DNA (related to toxicities for EC/FEC and docetaxel components, respectively, and given dose levels and outcome in relation to these factors and in relation QoL) to outcome per arm. 6. RFS analyzed in relation to tumour associated lymphocytes and Y-box binding protein in the comparison between the A- and B-arms. Tumour tissue will be obtained and stored for studies of prognostication and therapy prediction. Last patient randomized was September 2011.

Timeline

Start

2007-02

Primary completion

2016-04

Completion

2028-01

Publications

• Background Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet. 2019 Apr 6;393(10179):1440-1452. doi: 10.1016/S0140-6736(18)33137-4. Epub 2019 Feb 8.
• Results Matikas A, Papakonstantinou A, Loibl S, Steger GG, Untch M, Johansson H, Tsiknakis N, Hellstrom M, Greil R, Mobus V, Gnant M, Bergh J, Foukakis T. Benefit from dose-dense adjuvant chemotherapy for breast cancer: subgroup analyses from the randomised phase 3 PANTHER trial. Lancet Reg Health Eur. 2024 Dec 3;49:101162. doi: 10.1016/j.lanepe.2024.101162. eCollection 2025 Feb.
• Results Matikas A, Mobus V, Greil R, Andersson A, Steger GG, Untch M, Fornander T, Malmstrom P, Schmatloch S, Johansson H, Hellstrom M, Brandberg Y, Gnant M, Loibl S, Foukakis T, Bergh J; SweBCG, ABCSG and GBG. Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial. J Clin Oncol. 2024 Sep 10;42(26):3077-3082. doi: 10.1200/JCO.24.00178. Epub 2024 Jul 17.
• Results Zerdes I, Simonetti M, Matikas A, Harbers L, Acs B, Boyaci C, Zhang N, Salgkamis D, Agartz S, Moreno-Ruiz P, Bai Y, Rimm DL, Hartman J, Mezheyeuski A, Bergh J, Crosetto N, Foukakis T. Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study. NPJ Breast Cancer. 2021 Nov 19;7(1):144. doi: 10.1038/s41523-021-00352-3.
• Results Brandberg Y, Johansson H, Hellstrom M, Gnant M, Mobus V, Greil R, Foukakis T, Bergh J; Swedish Breast Cancer Group, the Austrian Breast, Colorectal Cancer Study Group, the German Breast Cancer Group. Long-term (up to 16 months) health-related quality of life after adjuvant tailored dose-dense chemotherapy vs. standard three-weekly chemotherapy in women with high-risk early breast cancer. Breast Cancer Res Treat. 2020 May;181(1):87-96. doi: 10.1007/s10549-020-05602-9. Epub 2020 Mar 31.
• Results Papakonstantinou A, Matikas A, Bengtsson NO, Malmstrom P, Hedayati E, Steger G, Untch M, Hubbert L, Johansson H, Hellstrom M, Gnant M, Loibl S, Greil R, Moebus V, Foukakis T, Bergh J. Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer: Results from the phase 3 PANTHER trial. Cancer. 2020 Mar 15;126(6):1175-1182. doi: 10.1002/cncr.32653. Epub 2019 Dec 18.
• Results Papakonstantinou A, Hedayati E, Hellstrom M, Johansson H, Gnant M, Steger G, Greil R, Untch M, Moebus V, Loibl S, Foukakis T, Bergh J, Matikas A. Neutropenic complications in the PANTHER phase III study of adjuvant tailored dose-dense chemotherapy in early breast cancer. Acta Oncol. 2020 Jan;59(1):75-81. doi: 10.1080/0284186X.2019.1670353. Epub 2019 Oct 4.
• Results Matikas A, Foukakis T, Moebus V, Greil R, Bengtsson NO, Steger GG, Untch M, Johansson H, Hellstrom M, Malmstrom P, Gnant M, Loibl S, Bergh J. Dose tailoring of adjuvant chemotherapy for breast cancer based on hematologic toxicities: further results from the prospective PANTHER study with focus on obese patients. Ann Oncol. 2019 Jan 1;30(1):109-114. doi: 10.1093/annonc/mdy475.
• Results Matikas A, Margolin S, Hellstrom M, Johansson H, Bengtsson NO, Karlsson L, Edlund P, Karlsson P, Lidbrink E, Linderholm B, Lindman H, Malmstrom P, Villman K, Foukakis T, Bergh J. Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer. Breast Cancer Res Treat. 2018 Apr;168(2):349-355. doi: 10.1007/s10549-017-4599-4. Epub 2017 Nov 30.
• Results Foukakis T, von Minckwitz G, Bengtsson NO, Brandberg Y, Wallberg B, Fornander T, Mlineritsch B, Schmatloch S, Singer CF, Steger G, Egle D, Karlsson E, Carlsson L, Loibl S, Untch M, Hellstrom M, Johansson H, Anderson H, Malmstrom P, Gnant M, Greil R, Mobus V, Bergh J; Swedish Breast Cancer Group (SweBCG), the German Breast Group (GBG), and the Austrian Breast & Colorectal Cancer Study Group (ABCSG). Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial. JAMA. 2016 Nov 8;316(18):1888-1896. doi: 10.1001/jama.2016.15865.
• Results Bergh J. Oral presentation, ASCO Annual Meeting 2016.
• Results Margolin S, Bengtsson NO, Carlsson L, Edlund P, Hellstrom M, Karlsson P, Lidbrink E, Linderholm B, Lindman H, Malmstrom P, Pettersson Skold D, Soderberg M, Villman K, Bergh J; Scandinavian Breast Group Study SBG 2004-1. A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer. Acta Oncol. 2011 Jan;50(1):35-41. doi: 10.3109/0284186X.2010.535847.

Drugs

Indications