Neo-/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 on pathological complete response (pCR) for patients treated within the neoadjuvant setting.

568 Background: GAIN-2 compares the effectiveness and safety of a predefined idd regimen (EnPC) vs. a dd regimen with modification of single doses depending on individual hematological and non-hematological toxicities (dtEC-dtD) as neo-/adjuvant treatment for patients with high risk breast cancer (BC) (NCT01690702). Methods: Patients with high risk BC (HER2+; triple negative BC (TNBC); luminal B-like: ER and/or PgR+, HER2-, Ki67 > 20%, N+; luminal A-like: ≥4 N+) were randomized to receive either iddEnPC (epirubicin 150mg/m2 q2w, nab-Paclitaxel 330mg/m2 q2w, cyclophosphamide 2000mg/m2 q2w for 3 cycles each) or dtEC-dtD (epirubicin 60-100mg/m2 and cyclophosphamide 450-1200mg/m2 q2w for 4 cycles followed by docetaxel 60-100mg/m2 q2w for 4 cycles). The primary objective of the trial is to compare the invasive disease-free survival (iDFS) between the two arms. pCR rates in the breast per arm (ypT0) in the neoadjuvant cohort will be reported. Results: In total the GAIN-2 trial accrued 2887 patients. From 08/2016 to 07/2017 598 patients have been randomized in the neoadjuvant setting (EnPC n = 298; dtEC-dtD n = 300). Median age was 49 [range 20-69] years. Overall, 2.3% had bilateral tumors, 38.0% cT1, 52.7% cT2 and 9.3% cT3/4, 55.4% cN+; 62.9% G3; 88.0% had Ki67 > 20%; 17.6% had hormone-receptor (HR)-positive/HER2-, 1.7% luminal A ≥4 N+, 31.9% HR+/ HER2+, 13.7% HR-/HER2+ and 35.1% TNBC. In the modified intention-to-treat population (EnPC n = 291; dtEC-dtD n = 293) the pCR rates for iddEnPC vs dtEC-dtD were 53.6% vs 45.1% (corrected continuity Chi-Square p = 0.047). Overall, 34.8% of the patients had at least 1 severe adverse event (EnPC 38.3% vs dtEC-dtD 31.3%). Conclusion: The GAIN-2 trials shows a statistically significant difference in terms of pCR rates within the breast for patients with high-risk BC receiving iddEnPC compared to dtEC-dtD as neoadjuvant chemotherapy. Further analyses are ongoing. Clinical trial information: NCT01690702.