Paoluzzi L, Cacavio A, Ghesani M, Karambelkar A, Rapkiewicz A, Weber J, Rosen G
Department of Medicine, NYU Langone Medical Center, New York, NY USA.
Department of Radiology, NYU Langone Medical Center, New York, NY USA.
Clin Sarcoma Res. 2016 Dec 30;6:24. doi: 10.1186/s13569-016-0064-0. eCollection 2016.
Manipulation of immune checkpoints such as CTLA4 or PD-1 with targeted antibodies has recently emerged as an effective anticancer strategy in multiple malignancies. Sarcomas are a heterogeneous group of diseases in need of more effective treatments. Different subtypes of soft tissue and bone sarcomas have been shown to express PD-1 ligand.
We retrospectively analyzed a cohort of patients (pts) with relapsed metastatic/unresectable sarcomas, who were treated with nivolumab provided under a patient assistance program from the manufacturer. Pts underwent CT or PET/CT imaging at baseline and after at least four doses of nivolumab; RECIST 1.1 criteria were used for response assessment.
Twenty-eight pts with soft tissue (STS, N = 24) or bone sarcoma (N = 4), received IV nivolumab 3 mg/kg every 2 weeks from July 2015. Median age was 57 (24-78), male:female ratio was 14:14; the median number of nivolumab cycles was eight. Eighteen pts concomitantly received pazopanib at 400-800 mg daily. The most common side effect was grade 1-2 LFT elevations; grade 3-4 toxicity occurred in five patients (colitis, LFT elevations, pneumonitis). Twenty-four pts received at least four cycles. We observed three partial responses: one dedifferentiated chondrosarcoma, one epithelioid sarcoma and one maxillary osteosarcoma (last two patients on pazopanib); nine patients had stable disease including three leiomyosarcomas; 12 patients had progression of disease including 4 leiomyosarcoma. Clinical benefit (response + stability) was observed in 50% of the evaluable patients.
These data provide a rationale for further exploring the efficacy of nivolumab and other checkpoint inhibitors in soft tissue and bone sarcoma.
使用靶向抗体操纵免疫检查点，如CTLA4或PD - 1，最近已成为多种恶性肿瘤中一种有效的抗癌策略。肉瘤是一组异质性疾病，需要更有效的治疗方法。软组织和骨肉瘤的不同亚型已被证明表达PD - 1配体。
我们回顾性分析了一组复发转移性/不可切除肉瘤患者，这些患者接受了制造商患者援助计划提供的纳武单抗治疗。患者在基线时以及至少接受四剂纳武单抗后接受CT或PET/CT成像；使用RECIST 1.1标准进行疗效评估。
2015年7月起，28例软组织肉瘤（STS，N = 24）或骨肉瘤（N = 4）患者每2周静脉注射3mg/kg纳武单抗。中位年龄为57岁（24 - 78岁），男女比例为14:14；纳武单抗治疗周期的中位数为8个。18例患者同时接受每日400 - 800mg的帕唑帕尼治疗。最常见的副作用是1 - 2级肝功能检查升高；5例患者出现3 - 4级毒性（结肠炎、肝功能检查升高、肺炎）。24例患者接受了至少四个周期的治疗。我们观察到3例部分缓解：1例去分化软骨肉瘤、1例上皮样肉瘤和1例上颌骨肉瘤（后两例患者接受帕唑帕尼治疗）；9例患者病情稳定，包括3例平滑肌肉瘤；12例患者病情进展，包括4例平滑肌肉瘤。50%的可评估患者观察到临床获益（缓解 + 稳定）。
这些数据为进一步探索纳武单抗和其他检查点抑制剂在软组织和骨肉瘤中的疗效提供了理论依据。
