Assessment of efficacy and safety of dose-dense doxorubicin and cyclophosphamide (ddAC) in combination with pembrolizumab in early-stage, triple-negative breast cancer.

e12618 Background: KEYNOTE-522 demonstrated significant improvement in pathologic complete response (pCR) and event free survival (EFS) for early stage triple negative breast cancer (TNBC) patients (pts) treated with pembrolizumab (PEMBRO) and chemotherapy (carboplatin/paclitaxel weekly followed by doxorubicin/cyclophosamide (AC) every 3 weeks) in the neo/adjuvant setting. Standard of care prior to KEYNOTE-522 was AC every 2 weeks (dd), however, implementation of ddAC becomes impractical when accommodating 21-day PEMBRO dosing and creates concern for compromised efficacy. KEYNOTE-555 demonstrated feasibility of every 6-week PEMBRO dosing. We modified the KEYNOTE-522 regimen to employ ddAC with PEMBRO every 6-weeks with the aim to maximize clinical outcomes while reducing time spent in the infusion center. The primary objective is to compare the rate of pCR using ddAC plus 6-week PEMBRO versus PEMBRO and AC every 3 weeks. Secondary objectives include: safety of concomitant chemoimmunotherapy by comparing the incidence of adverse events (AEs) with PEMBRO (every 3 or 6 weeks), assessing rates of held cycles or dose modifications, and assessing toxicity of concomitant capecitabine and PEMBRO in the adjuvant setting. Methods: This was a retrospective, single-center, cohort study at Duke University Hospital (DUH). Results reported via descriptive statistics. Adult pts with clinical stages I-III TNBC were included in this study. Pts must have completed four cycles of AC. Pre-specified data collection points were obtained from the electronic health record and entered into a secure database. Results: A total of 25 female pts treated at DUH were included. The rate of pCR was 64.3% (AC) versus 81.8% (ddAC). All patients experienced at least one adverse event with their immunochemotherapeutic regimen. The most common IO-induced toxicities included thyroid-associated AEs (37.5%) and rash (37.5%). There were no grade 3 or 4 IO-induced toxicities reported. Five patients were on concomitant adjuvant capecitabine and PEMBRO for residual disease. One patient in each arm required dose adjustments for capecitabine and 3 patients had at least one deferred cycle. One patient experienced AEs associated with capecitabine. No patients had toxicities attributable to adjuvant PEMBRO. Conclusions: In this small single center study, the administration of neoadjuvant ddAC with PEMBRO at 400mg every 6 weeks was deemed feasible with no excess toxicity. There was a trend towards improved efficacy for patients treated with ddAC with PEMBRO. Additionally, safety endpoints were similar between groups. This dosing strategy allows for optimization of therapy with the incorporation of ddAC and adjuvant capecitabine, thus potentially improving outcomes in TNBC patients. Larger cohort studies, in the real-world setting, are needed to confirm these findings.