Abstract PO4-13-06: Effect of neoadjuvant dose-dense dose-intense chemotherapy timing infusion on complete histological response rate among patients with triple negative breast cancer (SIMCLOCK)

Abstract

Abstract Background: Triple-negative breast cancers (TNBC) exhibit major responses to dose-dense, dose-intense (DD-DI) neoadjuvant chemotherapy (NAC) (1). Although chronomodulated chemotherapy has shown efficacy and reducing toxicity in other cancers, there are no data in breast cancers (2). We report here a series of patients with TNBC treated with DD-DI NAC and analyzed the association between chemotherapy time infusion and pathological complete response rate (pCR) and residual tumor burden (RCB). Patients and Methods: Patients with non-metastatic TNBC treated at breast cancer disease center, St Louis hospital (Paris, France), with neoadjuvant DD-DI cyclophosphamide (1200 mg/m2 d1) – epirubicin (75 mg/m2 d1) q2w (SIM regimen) followed by 12 injections of paclitaxel (80 mg/m2) qw were included. Starting time of each chemotherapy infusion were systematically recorded. Primary endpoint was pCR defined as no residual invasive tumor in breast and in lymph nodes. Patients were dichotomized into “morning” and “afternoon” infusion groups, independently for “SIM” and “paclitaxel” regimens. Two timing cut-offs were defined according to: 1) median time of all infusions 2) cut-off maximizing morning/afternoon differences of RCB. Statistical differences between the two patient groups were assessed for metabolic response at 2 courses at Pet scan (breast delta SUVmax), RCB class (0-1 vs 2-3), pCR, dose reduction rate and 24-months event-free survival (24-months EFS). Results: Between January 2018 and January 2022, 93 patients were included. Median age was 51 (28-74). Majority of SIM administrations occurred between 12:00 and 15:00 and Paclitaxel administrations between 11:20 and 14:30. Median follow-up was 32.4 months. Main characteristics between “morning group” or “afternoon” groups in the SIM or paclitaxel were similar. pCR was obtained in 48.9% of the whole population. Regardless of cut-offs defined, no difference in pCR rate was observed. Similarly, no differences were observed between morning and afternoon groups in terms of either metabolic response, dose reduction rate or 24-months EFS (table 1). Conclusion: Time of DD-DI NAC infusion is not associated with differences in pCR rate nor in RCB, toxicity and EFS in patients with early TNBC. As immunotherapy combined with NAC is a new standard in TNBC, the impact of immunotherapy infusion time combined with NAC is under evaluation.