Abstract PS13-51: A phase II study of neoadjuvant weekly carboplatin/paclitaxel followed by dose-dense doxorubicin/cyclophosphamide (DD AC)in patients with triple negative breast cancer (TNBC): Wisconsin oncology network (WON) study
Authors: Cheng Yee Chung , O'Regan Ruth , Chaudhary Lubna N , Kamaraju Sailaja , Einhorn Harvey , Sampene Emmanuel , Pigsley Marialane , Burkard Mark E , Chitambar Christopher R , Wisinski Kari B 
Published: February 2021

Abstract
Background: The CALGB 40603 and BrighTNess studies found that adding high dose carboplatin every 3 weeks to the standard neoadjuvant DD AC - paclitaxel regimen in TNBC increased the pathologic complete response (pCR) rate to 54-58% but with the cost of increased treatment related toxicities resulting in decreased completion of the full course of treatment. Our hypothesis is by changing the high dose carboplatin every 3 weeks to low dose weekly carboplatin, it will retain the same benefit in pathologic response rate and minimize the treatment related toxicities, which in turn permits the full course of neoadjuvant treatment given to patients. Patients and Methods: This multi-center study was conducted through the WON (NCT03301350). Eligible TNBC patients for neoadjuvant chemotherapy received weekly carboplatin (AUC=2) and paclitaxel 80 mg/m2 for 12 doses, followed by dose dense doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks with granulocyte growth factor support for 4 cycles. A one-week break was added before DD AC after the first 22 patients in order to minimize prolonged cytopenia. Primary end point was pCR. Secondary endpoints were frequency of dose modification and treatment related toxicities. Results: Accrual target was 50 with 80% power to detect a 20% difference using a one-sided binomial test at an alpha significance level of 0.025, but study was terminated earlier. Twenty-nine eligible patients consented for the study from November 2017 to February 2020. Median age was 52 year-old (range, 33-80). Twenty-eight patients received the study regimen. Three were removed due to early study termination and one (3.8%) died from grade 5 neutropenic sepsis after the last cycle of DD AC before surgery. Thus, 24 patients were evaluable for the primary outcome and 26 were evaluable for dose modification and toxicity outcomes. Eight patients (33%) achieved pCR and another 4 patients (17%) had minimal (ypT1aN0) residual disease. Of 26 patients, 24 (92%) were able to receive the full course of treatment +/- dose modification. One patient required the discontinuation of weekly carboplatin/paclitaxel completely due to severe infusion reaction and one did not finish the treatment before the study was terminated. Eight patients (31%) required dose delay with 5 of them during the weekly carboplatin/paclitaxel treatment. Seven patients (27%) also required dose reduction with 5 of them during the weekly carboplatin/paclitaxel treatment. Seventeen patients (65%) experienced severe adverse event (grade 3 or 4) with the majority of events (12/17) relating to grade 3-4 neutropenia or neutropenic fever. Conclusion: Although our study showed a lower pCR rate of 33% in compare to the previous CALGB 40603 (54%) and BrighTNess (58%) studies, we demonstrated that the majority of patients (92%) were able to receive the full course of study treatment. This weekly carboplatin with paclitaxel - AC regimen was used in the recent Keynote 522 study as the backbone chemotherapy to combine with check-point inhibitor immunotherapy in TNBC. However, any dosing schedules of carboplatin, weekly or every 3 weeks, add substantially to grade 3 or 4 toxicity of paclitaxel - AC. Aggressive supportive care management is needed when carboplatin is used.
Citation Format: Yee Chung Cheng, Ruth O'Regan, Lubna N Chaudhary, Sailaja Kamaraju, Harvey Einhorn, Emmanuel Sampene, Marialane Pigsley, Mark E Burkard, Christopher R Chitambar, Kari B Wisinski. A phase II study of neoadjuvant weekly carboplatin/paclitaxel followed by dose-dense doxorubicin/cyclophosphamide (DD AC)in patients with triple negative breast cancer (TNBC): Wisconsin oncology network (WON) study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-51.