• Nadia Harbeck, Oleg Gluz, Matthias Christgen, Ronald Ernest Kates, Michael Braun, Sherko Küemmel, Claudia Schumacher, Jochem Potenberg, Stefan Kraemer, Anke Kleine-Tebbe, Doris Augustin, Bahriye Aktas, Helmut Forstbauer, Joke Tio, Raquel von Schumann, Cornelia Liedtke, Eva-Maria Grischke, Johannes Schumacher, Rachel Wuerstlein, Hans Heinrich Kreipe, and Ulrike Anneliese Nitz.
• Nadia Harbeck, Ludwig Maximilians University Hospital of Munich; Michael Braun, Red Cross Hospital Munich; Rachel Wuerstlein, University Hospital Munich, Munich; Nadia Harbeck, Oleg Gluz, Ronald Ernest Kates, Rachel Wuerstlein, and Ulrike Anneliese Nitz, The West German Study Group; Oleg Gluz, Raquel von Schumann, and Ulrike Anneliese Nitz, Evangelical Hospital Bethesda, Mönchengladbach; Matthias Christgen and Hans Heinrich Kreipe, Hannover Medical School, Hannover; Sherko Küemmel, Kliniken Essen-Mitte; Bahriye Aktas, Essen University Hospital, Essen; Claudia Schumacher, St Elisabeth-Krankenhaus, Stefan Kraemer, University Clinic, Cologne; Jochem Potenberg, Evangelical Waldkrankenhaus, Anke Kleine-Tebbe, DRK Kliniken, Berlin; Doris Augustin, Clinic Deggendorf, Deggendorf; Helmut Forstbauer, Onkologie Rheinsieg, Troisdorf; Joke Tio, University Hospital Münster, Münster; Cornelia Liedtke, University of Lübeck, Lübeck; Eva-Maria Grischke, University Hospital of Tübingen, Tübingen; and Johannes Schumacher, Palleos Healthcare Services, Wiesbaden, Germany.
• J. Clin. Oncol. 2017 Sep 10; 35 (26): 3046-3054.

AbstractPurpose Human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen therapy-related severe adverse events (T-DM1 arms v trastuzumab plus ET; 5.3% v 3.1%, respectively) were reported. Conclusion The ADAPT HER2-positive/HR-positive trial demonstrates that neoadjuvant T-DM1 (with or without ET) given for only 12 weeks results in a clinically meaningful pCR rate. Thus, a substantial number of patients are spared the adverse effects of systemic chemotherapy.

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