Abstract P1-13-05: GAIN-2: Adjuvant phase III trial to compare intense dose-dense (idd) treatment with EnPC to tailored dose-dense (dt) therapy with dtEC-dtD for patients with high-risk early breast cancer: Results of the second safety interim analyses

Background: GAIN-2 compares the effectiveness and safety of a predefined intense dose-dense regimen (EnPC) vs. a dose-dense regimen with modification of single doses depending on individual hematological and non-hematological toxicities (dtEC-dtD) (NCT01690702). Moreover, the Trastuzumab substudy compares the subcutaneous administration of the drug to the abdominal wall vs. thigh. Methods: The primary objective of the GAIN-2 trial is to compare the invasive disease-free survival (iDFS) in patients with high-risk primary breast cancer (luminal A ≥4 N+; luminal B N+; HER2+ and TNBC N0/N+). Patients are randomized between EnPC ( epirubicin150 mg/m 2 q2w x 3, nab-Paclitaxel330 mg/m 2 q2w x 3, cyclophosphamide 2000 mg/m 2 q2w x 3) or dtEC-dtD (dd/tailored epirubicin/cyclophosphamide q2w x 4 followed by dd/tailored docetaxel q2w x 4) Two safety interim analyses after 200 (Noeding et al. Ann Oncol 2014) and 900 patients who have completed chemotherapy were planned. We present the results of the second safety analysis. In addition to the standard analyses for hematological and non-hematological toxicities, any affections of the cranial nerves as well as the rate of macula degenerations and anaphylactic reactionsare of special interest. Results: Between 09/2012 and 05/2015 a total of 1473 patients have been randomized (EnPC n=734; dtEC-dtD n=739). Among those, 84 patients have been included in the trastuzumab substudy. No safety data are currently available for the substudy. Median age was 52 years and median body-mass-index 26. In terms of hematological adverse events, the rate of febrile neutropeniagrade 3-4 (12% vs. 8%) and thrombopenia grade 3-4 (12% vs. 5%) was significantly increased in the EnPC arm. As for non-hematological side effects, there were significantly more patients developing an increase in alkaline phosphatase (59% vs. 40%), ALAT (69% vs. 59%), peripheral sensory neuropathy(83% vs. 68%), arthralgia (63% vs. 49%), myalgia(48% vs. 41%) and bone pain(25% vs. 17%) in the EnPC arm, whereas nosebleed(10% vs. 25%), edema (13% vs. 26%) and hand-foot syndrome (12% vs. 28%) were more common in the dtEC-dtD arm. We observed two treatment related deaths, both in the dtEC-dtD arm (cause of death: acute respiratory distress syndrome and pneumonia). There were no differences between the treatment arms for the toxicities of special interest. In the EnPC arm, overall 30% of the patients required dose-reductions due to hematological toxicities compared with only 10% in the dtEC-dtD arm (p 2 followed by docetaxel 100 mg/m 2 ) in more than one third of the patients receiving dtEC-dtD. In 9% of women a reduction was required in the 4th cycle of docetaxel. Conclusion: This interim safety analysis from a prospectively randomized trial investigating iddEnPC with predefined doses and a toxicity adapted idd/tailored strategy (dtEC-dtD) showed no additional or unexpected safety signals in the iddEnPC or dtEC-dtD arm. Therefore, no modifications in the conduction of the study are necessary and the study continues as expected. Citation Format: Mobus V, Luck H-J, Forstbauer H, Wachsmann G, Ober A, Schneeweiss A, Christensen B, von Abel E, Grischke E-M, Hoffkes H-G, Klare P, Yon-Dschun K, Schmatloch S, Furlanetto J, Burchardi N, von Minckwitz G, Loibl S. GAIN-2: Adjuvant phase III trial to compare intense dose-dense (idd) treatment with EnPC to tailored dose-dense (dt) therapy with dtEC-dtD for patients with high-risk early breast cancer: Results of the second safety interim analyses. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-13-05.