ABSTRACT Aim: Combined chemotherapy requires compromises in terms of dosage and treatment interval due to toxicities. The sequential administration of monotherapies allows high doses of single substances and dose-dense intervals. So far, such regimens have proved to be very effective in early breast cancer with high risk of recurrence. Nab-paclitaxel (nP) leads to a more favorable toxicity profile and greater efficacy compared with solvent-based taxanes. Methods: The GAIN2 study compares toxicity and efficacy of a pre-defined dose-dense high-dose regimen (EnPC) with a dose-dense regimen, where single doses are adjusted depending on individual haematological and non-haematological toxicities (dtEC-dtD). Primary endpoint is the invasive disease-free survival in patients with primary node-positive or high-risk node-negative breast cancer. Two safety interim analyses after 200 and 900 patients who have completed chemotherapy are planned. The results of the first safety analysis will be presented. In addition to the standard analyses for haematological and non-haematological toxicities, any affections of the cranial nerves as well as the rate of macular degeneration and anaphylactic reactions are of special interest. Results: In terms of hematological adverse events, the rate of febrile neutropenia grade 3-4 (14% vs. 5%) and thrombocytopenia grade 3-4 (14% vs. 5%) was significantly increased in the EnPC arm. As for the non-haematological side effects, there were significantly more patients developing anorexia (grade 1-4) in the EnPC arm. There were no differences between the treatment arms for the toxicities of special interest. In the EnPC arm, 28% required dose-reductions due to hematological toxicities compared with only 11% in the dtEC dtD arm (p = 0.002). The dose could be escalated to the maximum in half of the patients receiving dtEC dtD. In 7% of women a reduction was required in the 4th cycle of docetaxel. Conclusions: Due to similar toxicity profiles, the study will be continued without changes. Disclosure: A. Schneeweiss: Honoraria, Research Funding and Advisory Role: Celgene and Roche; G. von Minckwitz: Honoraria and Research Funding: Amgen, Celgene and Roche; V. Mobus: Honoraria and Research Funding: Amgen, GSK, Sanofi-Aventis, Pfizer, Roche. All other authors have declared no conflicts of interest.