E P Mamounas1, M Untch2, M S Mano3, C-S Huang4, C E Geyer5, G von Minckwitz6, N Wolmark7, X Pivot8, S Kuemmel9, M P DiGiovanna10, B Kaufman11, G Kunz12, A K Conlin13, J C Alcedo14, T Kuehn15, I Wapnir16, A Fontana17, J Hackmann18, J Polikoff19, M Saghatchian20, A Brufsky21, Y Yang22, M Zimovjanova23, T Boulet24, H Liu25, D Tesarowski26, L H Lam26, C Song26, M Smitt27, S Loibl28. 1. NSABP Foundation and; Department of Surgery, Orlando Health UF Health Cancer Center, Orlando, USA. Electronic address: terry.mamounas@orlandohealth.com. 2. AGO-B and Department of Gynecologic Oncology, HELIOS Klinikum Berlin Buch, Berlin, Germany. 3. Department of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil. 4. Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. 5. NSABP Foundation and; NSABP Foundation and Department of Internal Medicine, Division of Hematology and Medical Oncology, Houston Methodist Cancer Center, Houston, USA. 6. GBG, Neu-Isenburg, Germany. 7. NSABP Foundation and; NSABP Foundation and Department of Surgery, The University of Pittsburgh, Pittsburgh, USA. 8. ICANS, Strasbourg, France. 9. Breast Unit Kliniken Essen-Mitte, Essen, Germany; Klinik für Gynäkologie mit Brustzentrum Charité-Universitätsmedizin Berlin, Berlin, Germany. 10. Yale University School of Medicine, Yale Cancer Center and Smilow Cancer Hospital, New Haven, USA. 11. Oncology Division, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. 12. GBG, Neu-Isenburg, Germany; St. Johannes Hospital Dortmund, Dortmund, Germany. 13. NSABP Foundation and; NSABP Foundation and Department of Medical Oncology, Providence Cancer Institute, Portland, USA. 14. Department of Clinical Oncology, Centro Hemato Oncologico, Panama City, Panama. 15. AGO-B and Klinikum Esslingen, Esslingen, Germany. 16. NSABP Foundation and; NSABP Foundation and Stanford University School of Medicine, Stanford, USA. 17. Division of Medical Oncology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. 18. GBG, Neu-Isenburg, Germany; Marien-Hospital Witten, SEG, Witten, Germany. 19. NSABP Foundation and; NSABP Foundation and Department of Hematology/Oncology, Kaiser Permanente, San Diego, USA. 20. Breast Cancer Department, Institut Gustave Roussy, Villejuif, France. 21. NSABP Foundation and; NSABP Foundation and Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, USA. 22. Division of Hematology-Oncolog, Taichung Veterans General Hospital and School of Medicine, China Medical University, Taichung City, Taiwan. 23. Department of Oncology, Charles University and General University Hospital, Prague, Czech Republic. 24. Department of Biostatistics, F. Hoffmann-La Roche, Basel, Switzerland. 25. Product Development Safety, Genentech, Inc., South San Francisco, USA. 26. Product Development Oncology, Genentech, Inc., South San Francisco, USA. 27. Product Development Oncology, Genentech, Inc., South San Francisco, USA; Seattle Genetics, South San Francisco, USA. 28. GBG, Neu-Isenburg, Germany; Center for Haematology and Oncology Bethanien, Frankfurt, Germany.
Abstract
BACKGROUND: In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) afterneoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses. PATIENTS AND METHODS: KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing ataxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS). RESULTS: The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 arm (13.5% versus 3.8%), but there was no grade ≥3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT [hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67], non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.22-0.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence. CONCLUSIONS: T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.
RCT Entities:
BACKGROUND: In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses. PATIENTS AND METHODS: KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing a taxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS). RESULTS: The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 arm (13.5% versus 3.8%), but there was no grade ≥3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT [hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67], non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.22-0.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence. CONCLUSIONS:T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.
Authors: Nina Ditsch; Achim Wöcke; Michael Untch; Christian Jackisch; Ute-Susann Albert; Maggie Banys-Paluchowski; Ingo Bauerfeind; Jens-Uwe Blohmer; Wilfried Budach; Peter Dall; Eva Maria Fallenberg; Peter A Fasching; Tanja N Fehm; Michael Friedrich; Bernd Gerber; Oleg Gluz; Nadia Harbeck; Jörg Heil; Jens Huober; Hans H Kreipe; David Krug; Thorsten Kühn; Sherko Kümmel; Cornelia Kolberg-Liedtke; Sibylle Loibl; Diana Lüftner; Michael Patrick Lux; Nicolai Maass; Christoph Mundhenke; Ulrike Nitz; Tjoung-Won Park-Simon; Toralf Reimer; Kerstin Rhiem; Achim Rody; Marcus Schmidt; Andreas Schneeweiss; Florian Schütz; Hans-Peter Sinn; Christine Solbach; Erich-Franz Solomayer; Elmar Stickeler; Christoph Thomssen; Isabell Witzel; Volkmar Müller; Wolfgang Janni; Marc Thill Journal: Breast Care (Basel) Date: 2022-05-05 Impact factor: 2.268