■托里帕利马,一种新的PD-1抗体,被批准用于治疗多种实体瘤;然而,对于三阴性乳腺癌(TNBC)的新辅助化疗仍未评估.此外,诱导化疗后的新辅助免疫疗法降阶梯仍未充分开发。因此,我们进行了一项II期试验,研究了一种新的新辅助化学免疫治疗方案,包括对早期TNBC的免疫治疗降级.
■在2020年6月9日至2022年3月24日之间,在新辅助环境中,对组织学证实为II-III期TNBC的女性患者依次给予化疗和抗PD-1治疗。患者接受新辅助治疗,每2周使用4个周期的表柔比星-环磷酰胺,随后是toripalimab(240mg)每3周加上nab-紫杉醇每周一次,共12周。主要终点是总病理完全缓解(tpCR;ypT0/isypN0)。关键次要终点包括乳房pCR(bpCR;ypT0/is),无事件生存和生物标志物分析。还评估了安全性。本研究在ClinicalTrials.gov(NCT04418154)注册。
■在70名登记患者中(中位年龄,51年;62.9%,第三阶段),66完成治疗,无进展,随后接受手术。tpCR和bpCR患者的百分比为70例中的39例(55.7%,95%置信区间[CI]:43.3-67.6)和70人中的41人(58.6%,95%CI46.2-70.2),分别。16例(22.9%)患者出现≥3级不良事件(AE),常见的中性粒细胞减少(12,17.1%)和白细胞减少(11,15.7%)。最常见的免疫相关AE是甲状腺功能减退症(5,7.1%,所有1-2年级)。
■在新辅助化疗中包括12周的toripalimab在早期TNBC患者中赋予了令人鼓舞的活性和可控的毒性,这个方案值得进一步调查。
■国家自然科学基金,JunshiBiosciences,和江苏恒瑞医药。
UNASSIGNED: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC.
UNASSIGNED: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II-III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154).
UNASSIGNED: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3-67.6) and 41 of 70 (58.6%, 95% CI 46.2-70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1-2).
UNASSIGNED: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation.
UNASSIGNED: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.