Sherko Kuemmel, MD on Final Survival Results From the WSG ADAPT-HR+/HER2-Negative Chemotherapy Trial

Speaker 1: The ADAPT trial is one of the largest trial, where we focus on a de-escalation part, who needs chemotherapy without questions. And maybe in the high risk part, patients with chemotherapy is the best one. So if you summarize this, it's more than 5,600 patients are registered. In the first part, we registered the patients and all the patients are candidates for chemotherapy originally. And then we registered these patients, if the patients have an endocrine reduction therapy during the first three weeks. Afterwards, most of the patients had a surgery after this, or a re-biopsy. And if this patient has probably a Ki-67 response, so-called Ki-67 down regulation. And that situation means, if a Ki-67, probably from 20 or 30, going to 10 or less than 10, this is the Ki-67 response with endocrine therapy. Premenopausal, mostly Tamoxifen. Postmenopausal, mostly with aromatase inhibitors. If this happens, and together with an Oncotype DX test, they recurrent score is less than maybe 25, 12 to 25, these patients go directly to endocrine therapy alone. Or, maybe if the recurrent score was less than 12, this patient again goes directly to endocrine therapy. The second cohort, again, more than two and a half thousand patients are randomized in two different dose dense chemotherapy arms, containing anthracycline and taxanes. And one in the standard arm paclitaxel, four cycles every two weeks, with 175 milligram per meter square. On the experimental arm, now paclitaxel for eight cycles, 125 milligram per meter square. Both arms followed by biweekly anthracyclines and cyclophosphamides as dose dense fashion two. So this where the two randomized chemotherapy arms. The baseline characteristics of more than 2000 patients of these patients are well-balanced, directly coming in the chemotherapy arms are patients with high lymph node burden, or with [inaudible 00:02:26] score more than 25. And in comparison to the other cohort, patients with no endocrine response, if they have an Oncotype between 12 and 25. If you look at the two cohorts together, you see maybe half of the patients never get the chemotherapy, actually, candidates for chemotherapy, with Oncotype and P-67 response. Half of the patients maybe are high risk patients, and that suggests together, and get randomized through the chemotherapy. If we come to the conclusion of this 5,600 patients ADAPT trial, is first we establish that the combinations of clinical risk, genomic risk, and endocrine response, Ki-67 down regulations allows optimal patient selection for endocrine therapy or chemotherapy. The endocrine therapy alone, in lymph node negative up to three positive lymph node, has a distant disease-free survival for more than 96%, irrespective of age. The other cohort, where we have the randomization of the two taxanes, and the high-risk group of these patients, where we saw not paclitaxel, versus solvent-based paclitaxel in dose-dense sequential anthracycline taxanes chemotherapy regimen in HER two positive, HER two negative early breast cancer disease resulted in similar five-year IDFS distant disease-free survival over survival rates. Those taxane-based regimens have manageable safety profiles and low discontinuation rates, and can be considered as standard chemotherapy options for maybe high-risk HR positive HER-2 negative early breast cancer disease patients.