S Loibl1, C Jackisch2, A Schneeweiss3, S Schmatloch4, B Aktas5, C Denkert6, H Wiebringhaus7, S Kümmel8, M Warm9, S Paepke10, M Just11, C Hanusch12, J Hackmann13, J-U Blohmer14, M Clemens15, S Dan Costa16, B Gerber17, K Engels18, V Nekljudova1, G von Minckwitz1, M Untch19. 1. German Breast Group, Neu-Isenburg, , Germany 2. Department of Obstetrics & Gynecology, Sana Klinikum, Offenbach, Germany. 3. National Center for Tumor Diseases, University Hospital, Heidelberg, , Germany. 4. Breast Cancer Center, Elisabeth Krankenhausx, Weinbergstraße 7, Kassel, Germany. 5. Department of Gynecology & Obstetrics, University Women's Hospital Essen, Essen, Germany. 6. Department of Pathology, University Hospital Charité, Berlin, Germany. 7. Gynecology, St. Barbara-Klinik Hamm-Heessen, Hamm, Germany. 8. Breast Unit, Interdisziplinäres Brustzentrum an den Kliniken Essen-Mitte, Essen, Germany. 9. Breast Unit, Brustzentrum im Krankenhaus Köln-Holweide, Köln, Germany. 10. Women's Clinic, Klinikum Rechts der Isar der TU München, Klinik und Poliklinik für Frauenheilkunde, München, Germany. 11. Oncology, Onkologische Schwerpunktpraxis Bielefeld, Germany. 12. Women's Clinic, Klinikum zum Roten Kreuz, München, Germany. 13. Breast Unit, Marien Hospital Witten, Witten, Germany. 14. Women's Clinic, Klinik für Gynäkologie am Campus Charité Mitte, Berlin, Germany. 15. Women's Clinic, Klinikum Mutterhaus der Borromäerinnen, Trier, Germany. 16. Department of Gynecology, Universitäts-Frauenklinik, Magdeburg, Germany. 17. Women's Clinic, Universitäts-Frauenklinik, Rostock, Germany. 18. Department of Pathology, Zentrum für Pathologie, Zytologie und Molekularpathologie Neuss, Germany. 19. Department of Gynecology and Obstetrics, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
Abstract
Background: The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort. Patients and methods: Patients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0. Results: Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%, P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3-4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline. Conclusion: In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane-epirubicin-cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.
RCT Entities:
Background: The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort. Patients and methods: Patients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0. Results: Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%, P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3-4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline. Conclusion: In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane-epirubicin-cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.
Authors: Tessa G Steenbruggen; Mette S van Ramshorst; Marleen Kok; Sabine C Linn; Carolien H Smorenburg; Gabe S Sonke Journal: Drugs Date: 2017-08 Impact factor: 9.546
Authors: Ramon Colomer; Cristina Saura; Pedro Sánchez-Rovira; Tomás Pascual; Isabel T Rubio; Octavio Burgués; Lourdes Marcos; César A Rodríguez; Miguel Martín; Ana Lluch Journal: Oncologist Date: 2019-02-01
Authors: O Ortmann; J-U Blohmer; N T Sibert; S Brucker; W Janni; A Wöckel; A Scharl; S Dieng; J Ferencz; E C Inwald; S Wesselmann; C Kowalski Journal: J Cancer Res Clin Oncol Date: 2022-04-05 Impact factor: 4.553
Authors: Santiago González-Santiago; Cristina Saura; Eva Ciruelos; José Luis Alonso; Pilar de la Morena; Marta Santisteban Eslava; Maria Isabel Gallegos Sancho; Alicia de Luna; Elsa Dalmau; Sonia Servitja; Manuel Ruiz Borrego; José Ignacio Chacón Journal: Breast Cancer Res Treat Date: 2020-09-02 Impact factor: 4.872
Authors: Mariana Brandão; Rafael Caparica; Luca Malorni; Aleix Prat; Lisa A Carey; Martine Piccart Journal: Clin Cancer Res Date: 2020-02-11 Impact factor: 12.531