Andreas Schneeweiss1, Volker Möbus2, Hans Tesch3, Claus Hanusch4, Carsten Denkert5, Kristina Lübbe6, Jens Huober7, Peter Klare8, Sherko Kümmel9, Michael Untch10, Karin Kast11, Christian Jackisch12, Jörg Thomalla13, Barbara Ingold-Heppner5, Jens-Uwe Blohmer5, Mahdi Rezai14, Matthias Frank15, Knut Engels16, Kerstin Rhiem17, Peter Andreas Fasching18, Valentina Nekljudova19, Gunter von Minckwitz19, Sibylle Loibl20. 1. National Center for Tumor Diseases (NCT) Heidelberg, Germany. 2. Department of Gynaecology and Obstetrics, Clinic Frankfurt-Hoechst, Germany. 3. Praxis Bethanien, Frankfurt, Germany. 4. Clinic of Red Cross, Munich, Germany. 5. Charité University Hospital Berlin, Germany. 6. Henriettenstiftung Hannover, Germany. 7. University Hospital Ulm, Germany. 8. Praxisklinik Krebsheilkunde für Frauen Berlin, Germany. 9. Breast Center, Clinic Essen-Mitte, Germany. 10. HELIOS Clinic Berlin-Buch, Germany. 11. University Hospital Dresden, Germany. 12. Sana-Clinic Offenbach, Germany. 13. Clinic for Haematology and Oncology Koblenz, Germany. 14. Medical Center, Luisenkrankenhaus Düsseldorf, Germany. 15. Ortenau Clinics, Germany. 16. Zentrum für Pathologie, Zytologie und Molekularpathologie Neuss, Germany. 17. ClinicCenter for Familial Breast and Ovarian Cancer, University Hospital of Cologne, Germany. 18. Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Germany. 19. German Breast Group, Neu-Isenburg, Germany. 20. Praxis Bethanien, Frankfurt, Germany; German Breast Group, Neu-Isenburg, Germany. Electronic address: sibylle.loibl@gbg.de.
Abstract
BACKGROUND: GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet®) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC). PATIENTS AND METHODS: Patients with cT1c-cT4a-d and centrally assessed human epidermal growth factor receptor (HER)2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pN+. Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m2) followed by P (225 mg/m2) followed by C (2000 mg/m2), each q2w for 3 cycles or weekly P (80 mg/m2) plus M (20 mg/m2) plus, in TNBC, Cb (area under curve (AUC) 1.5). HER2-positive BC patients additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Primary end-point was pathological complete response (pCR, ypT0/is ypN0), secondary end-points included other pCR definitions, pCR in stratified subpopulations, tolerability and compliance. This trial is registered with ClinicalTrials.gov number NCT02125344. RESULTS: 945/961 randomised patients started treatment. The median age was 48 years; 7.6% had cT3-4, 46% cN+, 66% G3, 40% HER2-positive, 43% TNBC. pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77-1.28, P = 0.979) with no significant differences observed in TNBC, HER2-positive, luminal B-like subtypes. 16.4% with iddEPC and 34.1% with PM(Cb) discontinued treatment (P < 0.001), mainly due to adverse events; two patients on PM(Cb) died. CONCLUSIONS: In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. iddEPC is one of the effective dose-dense regimens feasible in daily practice.
RCT Entities:
BACKGROUND: GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet®) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC). PATIENTS AND METHODS: Patients with cT1c-cT4a-d and centrally assessed humanepidermal growth factor receptor (HER)2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pN+. Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m2) followed by P (225 mg/m2) followed by C (2000 mg/m2), each q2w for 3 cycles or weekly P (80 mg/m2) plus M (20 mg/m2) plus, in TNBC, Cb (area under curve (AUC) 1.5). HER2-positive BC patients additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Primary end-point was pathological complete response (pCR, ypT0/is ypN0), secondary end-points included other pCR definitions, pCR in stratified subpopulations, tolerability and compliance. This trial is registered with ClinicalTrials.gov number NCT02125344. RESULTS: 945/961 randomised patients started treatment. The median age was 48 years; 7.6% had cT3-4, 46% cN+, 66% G3, 40% HER2-positive, 43% TNBC. pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77-1.28, P = 0.979) with no significant differences observed in TNBC, HER2-positive, luminal B-like subtypes. 16.4% with iddEPC and 34.1% with PM(Cb) discontinued treatment (P < 0.001), mainly due to adverse events; two patients on PM(Cb) died. CONCLUSIONS: In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. iddEPC is one of the effective dose-dense regimens feasible in daily practice.
Authors: Kuo Chen; Jin Zhang; Narasimha M Beeraka; Chengyun Tang; Yulia V Babayeva; Mikhail Y Sinelnikov; Xinliang Zhang; Jiacheng Zhang; Junqi Liu; Igor V Reshetov; Olga A Sukocheva; Pengwei Lu; Ruitai Fan Journal: Front Oncol Date: 2022-06-22 Impact factor: 5.738