医学
阿替唑单抗
紫杉醇
内科学
肿瘤科
三阴性乳腺癌
化疗
临床终点
乳腺癌
新辅助治疗
人口
多西紫杉醇
临床研究阶段
卡铂
蒽环类
临床试验
化疗方案
癌症
免疫疗法
彭布罗利珠单抗
环境卫生
作者
Peter Schmid,F.J. Salvador Bofill,Begoña Bermejo,Mark M. Phillips,Denys N. Wheatley,F. Neus,Christian Schem,Agostina Stradella,Marcello Mele,A. Cortes Salgado,Vanesa Quiroga,Antoni Torres,A. Llombart Cussac,Elisabet Zamora,Giuseppe Viale,S. Kuemmel,Andrew J. Prendergast,Kelly Mousa,Oleg Gluz,Juan Carlos Cortés
标识
DOI:10.1016/j.annonc.2021.08.404
摘要
Pathological complete response (pCR) to neoadjuvant treatment in TNBC is strongly correlated with improved EFS and OS. Randomised trials have demonstrated increased pCR rates with the addition of checkpoint inhibitors to NACT in TNBC. Preclinical evidence suggests that AKT inhibition can enhance checkpoint inhibitor efficacy. The AKT inhibitor ipatasertib (IPAT) has shown promising activity in combination with paclitaxel as 1L therapy for metastatic TNBC. BARBICAN was designed to evaluate the clinical and biological effects of adding IPAT to NACT plus atezolizumab (atezo). International phase II, randomised trial in 146 patients (pts) with newly diagnosed, non-metastatic, high risk (node+ and/or tumour size ≥2 cm) TNBC. Patients were randomised (1:1) to receive one cycle of atezo (1200mg Q3W) ± IPAT (400mg D1-14), followed by 3 cycles of atezo (840mg Q2W) + weekly paclitaxel (80mg/m2) ± IPAT (400mg D1-21), followed by 4 cycles of atezo (840mg Q2W) + dose-dense doxorubicin (60mg/m2)/cyclophosphamide (600 mg/m2). Tumour biopsies were obtained at baseline, after each treatment phase and surgery. The primary clinical endpoint was pCR rate (ypT0/is ypN0). PD-L1 expression was assessed using the SP142 assay (1% cut-off). 144 pts received treatment, IPAT (n = 72) vs no ipatasertib (no-IPAT) (n = 72). There was no difference in pCR rates between treatment groups (chemo/atezo + IPAT, 49.3%, 95%CI, 36.8%-61.8%; chemo/atezo alone, 48.5%, 95%CI, 36.2%-61.0%). For IPAT vs no-IPAT, pCR was 66.7% vs 75.0% in the PD-L1-positive population (65 pts) and 32.4% vs 25.0% in the PD-L1-negative population (70 pts). pCR in node-positive pts was 55.6% (IPAT, 51.6%, no-IPAT 59.4%) compared to 43.1% (IPAT, 47.2%, no-IPAT 38.9%) in node-negative pts. Grade 3 or higher AE rates were 73.6% in the chemo/atezo + IPAT group and 40.3% in the chemo/atezo alone group, with rash, neutropenia, ALT increase, diarrhoea and mucosits being the most common. The majority of patients required IPAT dose modifications and the dose intensity was low. Addition of IPAT to neoadjuvant atezo plus chemotherapy did not improve pCR rates. IPAT dose intensity was low due to increased toxicity.