Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA
Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
J Immunother Cancer. 2020 Feb;8(1). doi: 10.1136/jitc-2019-000173.
Response rates to single agent immune checkpoint blockade in unselected pretreated HER2-negative metastatic breast cancer (MBC) are low. However, they may be augmented when combined with chemotherapy.
We conducted a single-arm, phase II study of patients with triple negative (TN) or hormone receptor-positive endocrine-refractory (HR+) MBC who were candidates for capecitabine. Patients were treated with pembrolizumab 200 mg intravenously day 1 and capecitabine 1000 mg/m by mouth twice daily on days 1-14 of a 21-day cycle. The primary end point was median progression-free survival (mPFS) compared with historic controls and secondary end points were overall response rate (ORR), safety and tolerability. The study had 80% power to detect a 2-month improvement in mPFS with the addition of pembrolizumab over historic controls treated with capecitabine alone.
Thirty patients, 16 TN and 14 HR+ MBC, were enrolled from 2017 to 2018. Patients had a median age of 51 years and received a median of 1 (range 0-6) prior lines of therapy for MBC. Of 29 evaluable patients, the mPFS was 4.0 (95% CI 2.0 to 6.4) months and was not significantly longer than historic controls of 3 months. The median overall survival was 15.4 (95% CI 8.2 to 20.3) months. The ORR was 14% (n=4), stable disease (SD) was 41% (n=12) and clinical benefit rate (CBR=partial response+SD>6 months) was 28% (n=8). The ORR and CBR were not significantly different between disease subtypes (ORR 13% and 14%, CBR 25% and 29% for TN and HR+, respectively). The 1-year PFS rate was 20.7% and three patients have ongoing responses. The most common adverse events were low grade and consistent with those seen in MBC patients receiving capecitabine, including hand-foot syndrome, gastrointestinal symptoms, fatigue and cytopenias. Toxicities at least possibly from pembrolizumab included grade 3 or 4 liver test abnormalities (7%), rash (7%) and diarrhea (3%), as well as grade 5 hepatic failure in a patient with liver metastases.
Compared with historical controls, pembrolizumab with capecitabine did not improve PFS in this biomarker unselected, pretreated cohort. However, some patients had prolonged disease control.
NCT03044730.
未经选择的预处理 HER2 阴性转移性乳腺癌（MBC）患者使用单一药物免疫检查点阻断的反应率较低。然而，当与化疗联合使用时，反应率可能会提高。
我们进行了一项单臂、二期研究，纳入了适合接受卡培他滨治疗的三阴性（TN）或激素受体阳性内分泌难治性（HR+）MBC 患者。患者接受静脉注射 200mg 培布利珠单抗，每日 1 次，卡培他滨 1000mg/m，每日 2 次，于 21 天周期的第 1-14 天口服。主要终点是与历史对照相比，中位无进展生存期（mPFS），次要终点是总缓解率（ORR）、安全性和耐受性。该研究有 80%的效能，可检测出与单独接受卡培他滨治疗的历史对照相比，mPFS 增加 2 个月。
2017 年至 2018 年期间，共招募了 30 名患者，其中 16 名为 TN MBC，14 名为 HR+ MBC。患者的中位年龄为 51 岁，接受 MBC 治疗的中位数为 1 线（范围 0-6 线）。在 29 名可评估的患者中，mPFS 为 4.0（95%CI 2.0 至 6.4）个月，与历史对照的 3 个月相比，并无明显延长。中位总生存期为 15.4（95%CI 8.2 至 20.3）个月。ORR 为 14%（n=4），疾病稳定（SD）为 41%（n=12），临床获益率（CBR=部分缓解+SD>6 个月）为 28%（n=8）。疾病亚型之间的 ORR 和 CBR 无明显差异（ORR 分别为 13%和 14%，CBR 分别为 25%和 29%，TN 和 HR+）。1 年 PFS 率为 20.7%，3 名患者仍有持续缓解。最常见的不良反应为低级别，与接受卡培他滨治疗的 MBC 患者一致，包括手足综合征、胃肠道症状、疲劳和血液学毒性。至少可能与培布利珠单抗相关的毒性包括 3 级或 4 级肝试验异常（7%）、皮疹（7%）和腹泻（3%），以及一名肝转移患者发生 5 级肝衰竭。
与历史对照相比，在未经生物标志物选择的预处理队列中，培布利珠单抗联合卡培他滨并未改善 PFS。然而，一些患者的疾病控制得到了延长。
NCT03044730。
