Safety and tolerability of adjuvant combination treatments following KEYNOTE-522 for early-stage or locally advanced breast cancer with residual disease.

IntroductionPatients with residual invasive carcinoma after neoadjuvant chemotherapy (NACT) for early-stage breast cancer have poor prognoses. The primary objective of this study was to assess the safety and tolerability of adjuvant combination regimens in patients with residual disease after KEYNOTE-522 NACT and surgery.MethodsPatients ≥ 18 years old with triple-negative or hormone-receptor low positive early-stage breast cancer were included if treated with KEYNOTE-522 NACT (modified to dose-dense doxorubicin plus cyclophosphamide (ddAC) in most patients). After definitive surgery, patients were assessed for residual disease and whether they received adjuvant capecitabine or a poly ADP ribose polymerase (PARP) inhibitor concurrently with pembrolizumab or sequentially after pembrolizumab. Adverse effects and dose modifications were collected.ResultsTwenty-two patients received concurrent treatment and eight received sequential treatment. Higher rates of toxicity occurred when two adjuvant agents were administered concurrently compared to sequentially (p-value = 0.166). The concurrent group also had more capecitabine dose adjustments (50% vs. 37.5%), doses held (36.4% vs. 25%) and discontinuations (9.1% vs. 0%) as well as pembrolizumab discontinuations (13.67% vs. 0%). The pathologic complete response (pCR) rates were higher with the use of ddAC than with every-3-weeks doxorubicin plus cyclophosphamide (AC) administered in KEYNOTE-522 (84.7% vs. 64.8%).ConclusionConcurrent therapy with pembrolizumab and capecitabine or olaparib trended towards demonstrating more toxicities than sequential therapy, though not statistically significant. However, concurrent therapy can be completed with dose adjustments or holds per patient tolerability. Additionally, our findings suggest modifying NACT KEYNOTE-522 to ddAC may improve response rates over traditional NACT KEYNOTE-522.