Ahmed Kamran A, Kim Youngchul, Arrington John A, Kim Sungjune, DeJesus Michelle, Soyano Aixa E, Armaghani Avan J, Costa Ricardo L B, Khong Hung T, Loftus Loretta S, Rosa Marilin, Caudell Jimmy J, Diaz Roberto, Robinson Timothy J, Etame Arnold B, Tran Nam D, Sahebjam Solmaz, Soliman Hatem H, Czerniecki Brian J, Forsyth Peter A, Yu H Michael, Han Hyo S
Departments of Radiation Oncology.
Biostatistics and Bioinformatics.
Adv Radiat Oncol. 2021 Sep 11;6(6):100798. doi: 10.1016/j.adro.2021.100798. eCollection 2021 Nov-Dec.
We hypothesize treatment with nivolumab and stereotactic radiosurgery (SRS) will be feasible and well tolerated, and may improve intracranial tumor control rates compared with SRS alone.
The study was designed as a prospective, single-arm, nonrandomized, open-label, phase 1b trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Key eligibility criteria included patients with breast cancer brain metastases of all subtypes, age ≥18, Eastern Cooperative Oncology Group Performance Status ≤2 with ≤10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg intravenously) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. This study is closed to accrual and is registered with ClinicalTrials.gov, NCT03807765.
Between February 2019 and July 2020, a total of 12 patients were treated to 17 lesions. No dose limiting toxicities were noted in our patient population. The most common neurologic adverse events included grade 1 to 2 headaches and dizziness occurring in 5 (42%) of patients. Median intracranial control was 6.2 months (95% confidence interval, 3-14 months) with 6- and 12-month control rates of 55% and 22%, respectively. A total of 4 patients had systemic progression during the study. Median time to systemic progression free survival has not been reached with 6- and-12 month rates of 63% and 51%, respectively.
Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. Preliminary data reveals activity in certain breast cancer patients to study therapy.
我们假设，与单纯立体定向放射外科手术（SRS）相比，纳武单抗联合SRS治疗将是可行的，耐受性良好，并且可能提高颅内肿瘤控制率。
本研究设计为一项前瞻性、单臂、非随机、开放标签的1b期试验，纳入患有转移性乳腺癌脑转移的患者，给予纳武单抗和SRS治疗。主要入选标准包括所有亚型的乳腺癌脑转移患者、年龄≥18岁、东部肿瘤协作组体能状态≤2且脑转移灶≤10个。治疗起始剂量为纳武单抗（静脉注射480mg），每4周重复一次。在纳武单抗初始剂量给药1周后进行SRS。本研究已停止入组，并在ClinicalTrials.gov注册，注册号为NCT03807765。
2019年2月至2020年7月期间，共有12例患者的17个病灶接受了治疗。在我们的患者群体中未观察到剂量限制性毒性。最常见的神经系统不良事件包括1至2级头痛和头晕，5例（42%）患者出现此类症状。颅内控制的中位时间为6.2个月（95%置信区间，3 - 14个月），6个月和12个月的控制率分别为55%和22%。共有4例患者在研究期间出现全身进展。全身无进展生存的中位时间尚未达到，6个月和12个月的无进展生存率分别为63%和51%。
纳武单抗联合SRS是乳腺癌脑转移的一种安全可行的治疗选择。初步数据显示该疗法在某些乳腺癌患者中具有活性。
