Abstract PO2-03-12: Dose-Dense Doxorubicin plus Cyclophosphamide (ddAC) and Impact of Chemotherapy Sequence in a Modified KEYNOTE-522 Regimen for Neoadjuvant Treatment of Triple Negative Breast Cancer: Real World Experience
Authors: Mai Nicholas , Myers Sara , Shen Sherry , Downs-Canner Stephanie , Chen Yuan , Traina Tiffany , Abuhadra Nour 
Published: May 2024

Background:

Standard of care systemic treatment for early stage triple negative breast cancer (TNBC) consists of neoadjuvant chemoimmunotherapy based upon the results of KEYNOTE 522 (KN-522). The KN522 regimen utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has shown superior OS compared to q3week AC in anthracycline and taxane-based regimens (per CALGB 9741 and EBCTCG analyses). We now present a retrospective study of patients treated with ddAC in a modified KN-522 regimen and report real world feasibility, safety, and efficacy endpoints, including exploration of whether sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab impacts outcome.

Methods:

Patients with TNBC treated at MSK from August 2021 to September 2022 with a preoperative KN-522 regimen were eligible for inclusion. Clinicopathological and demographic data were obtained from chart review. The primary goal of this study was to describe pathologic complete response (PCR) rate, incidence of treatment-related toxicities resulting in treatment delays, and type of toxicity. Treatment delays for toxicity were defined as a &gt;1 week delay in treatment or discontinuation of a treatment regimen component due to a medical reason. Exploratory analysis was conducted to assess efficacy and toxicity of ddAC before or after CbT as well as rate of GCSF usage with CbT. Baseline characteristics, incidence and type of delays, and treatment outcomes were compared between ddAC first and CbT first using two sample non-parametric tests.

Results:

129 TNBC patients met eligibility as defined above. Median age of diagnosis was 50. Clinical stage at diagnosis: Stage I 6%, Stage II 83%, and Stage III 11%. 128 patients received ddAC and 1 patient received AC q3week. Of the 128 patients, 54% received ddAC first while 46% received CbT first. Overall PCR rate of 56%. Treatment-related toxicity leading to chemotherapy delays was 61% and immunotherapy delays was 30%. Most chemotherapy delays were due to cytopenias (79%), with neutropenia (66%) most common. Adrenal insufficiency (4%) and hepatitis (5%) were the most common immune-related toxicities leading to delays. Overall, PCR rate was not affected by chemotherapy delays (No Delay 50% vs. Delay 60%, RR 0.83, 95%CI 0.60-1.15, p=0.25) or immunotherapy delays (No Delay 56% vs. Delay 58%, RR 0.96, 95%CI 0.69-1.33, p=0.81). Exploratory analysis comparing sequencing of ddAC vs CbT first showed incidence of CbT delays was 58% in patients treated with ddAC first and 27% in CbT first. Incidence of ddAC delays was 3% in patients treated with ddAC first and 7% in CbT first. Incidence of delays in both ddAC and CbT was 9% in ddAC first and 10% in CbT first. There was no difference in PCR rate (ddAC 55% vs. CbT 58%, RR 0.96, 95%CI 0.70-1.30, p=0.77) or rate of immunotherapy delays (ddAC 32% vs. CbT 34%, RR 0.93, 95%CI 0.55-1.57, p=0.79) based on sequence of chemotherapy. However, ddAC first compared to CbT first correlated with a significant increase in the incidence of overall treatment delays (ddAC 70% vs. CbT 51%, RR 1.37, 95%CI 1.02-1.84, p=0.03), use of GCSF during CbT (ddAC 55% vs. CbT 34%, RR 1.60, 95%CI 1.06-2.45, p=0.02), and treatment-limiting cytopenias at any time point before surgery (ddAC 59% vs. CbT 31%, RR 1.95, 95%CI 1.26-3.00, p=0.001).

Conclusions:

These real world data support the feasibility and tolerability of ddAC in a modified KN522 regimen. Exploratory analysis on sequencing of ddAC vs. CbT first in this regimen suggests that efficacy is comparable, yet ddAC first is significantly associated with higher rates of treatment delays and cytopenias. Overall, our experience suggests ddAC is a safe and viable modification to KN-522, and sequencing ddAC after CbT may reduce the risk of treatment induced cytopenias.

Citation Format: Nicholas Mai, Sara Myers, Sherry Shen, Stephanie Downs-Canner, Yuan Chen, Tiffany Traina, Nour Abuhadra. Dose-Dense Doxorubicin plus Cyclophosphamide (ddAC) and Impact of Chemotherapy Sequence in a Modified KEYNOTE-522 Regimen for Neoadjuvant Treatment of Triple Negative Breast Cancer: Real World Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-03-12.