Kataria Babita, Sharma Aparna, Biswas Bivas, Bakhshi Sameer, Pushpam Deepam
Department of Medical Oncology, National Cancer Institute, Badsa, Jhajjar, Haryana, 124105, India.
Department of Medical Oncology, All India Institute of Medical Sciences, Ansari Nagar East, New Delhi, 110029, India.
Ecancermedicalscience. 2021 Sep 2;15:1281. doi: 10.3332/ecancer.2021.1281. eCollection 2021.
Uncommon histopathological subtypes account for less than 5% cases of soft tissue sarcoma (STS) and unclassified STSs comprise another 16%, these are often chemotherapy-resistant, with a dismal outcome in unresectable/metastatic disease. Prospective studies on the use of pazopanib in this cohort of patients are lacking in the literature. Here, we describe the safety and efficacy of pazopanib in rare histologies of advanced STS.
We conducted a retrospective study at two tertiary cancer centres in India, evaluating 33 cases of rare subtypes of STS, who received pazopanib as per institutional protocol between January 2013 and December 2019. Patients who received pazopanib for unresectable/metastatic disease were enrolled in this study for clinicopathologic features, treatment outcome and evaluation of prognostic factors.
Out of 33 patients, there were seven cases of undifferentiated pleomorphic sarcoma, four cases each of myxofibrosarcoma, epithelioid sarcoma and malignant peripheral nerve sheath tumour, three cases each of haemangiopericytoma and spindle cell sarcoma, two cases of haemangioendothelioma and a case each of clear cell sarcoma, retroperitoneal sarcoma, angiosarcoma and pleomorphic rhabdomyosarcoma-adult type. The objective response rate was 27%. Most of the patients (67%) received pazopanib in second or subsequent lines of therapy. The majority (70%) were started at a lower dose of 400/600 mg and only 43% of these (10/23) could be escalated to a full dose of 800 mg based on tolerance. On univariate analysis, pazopanib's starting dose didn't predict progression-free survival (PFS)/overall survival (OS)/response rate. At a median duration of follow-up of 18.8 months (range 1.9-150.4 months), the median PFS and median OS were 10.3 months (95% confidence interval (CI): 5.9-14.8) and 17.8 months (95% CI: 10.7-29.3), respectively. 27% of the patients experienced grade ¾ toxicities, 12% required dose modification of pazopanib and 21% needed permanent discontinuation due to toxicity.
Our study shows that pazopanib is active in rare subtypes of STS.
罕见组织病理学亚型的软组织肉瘤（STS）病例占比不到5%，未分类的STS病例占另外的16%，这些病例通常对化疗耐药，不可切除/转移性疾病的预后很差。文献中缺乏关于帕唑帕尼在这类患者中的前瞻性研究。在此，我们描述了帕唑帕尼在晚期STS罕见组织学类型中的安全性和有效性。
我们在印度的两家三级癌症中心进行了一项回顾性研究，评估了33例STS罕见亚型病例，这些患者在2013年1月至2019年12月期间按照机构方案接受了帕唑帕尼治疗。因不可切除/转移性疾病接受帕唑帕尼治疗的患者纳入本研究，以评估其临床病理特征、治疗结果和预后因素。
33例患者中，有7例未分化多形性肉瘤，黏液纤维肉瘤、上皮样肉瘤和恶性外周神经鞘瘤各4例，血管外皮细胞瘤和梭形细胞肉瘤各3例，血管内皮瘤2例，透明细胞肉瘤、腹膜后肉瘤、血管肉瘤和成人型多形性横纹肌肉瘤各1例。客观缓解率为27%。大多数患者（67%）在二线或后续治疗中接受了帕唑帕尼治疗。大多数患者（70%）开始时使用较低剂量的400/600mg，其中只有43%（10/23）的患者能够根据耐受性增加至800mg的全剂量。单因素分析显示，帕唑帕尼的起始剂量不能预测无进展生存期（PFS）/总生存期（OS）/缓解率。中位随访时间为18.8个月（范围1.9 - 150.4个月），中位PFS和中位OS分别为10.3个月（95%置信区间（CI）：5.9 - 14.8）和17.8个月（95%CI：10.7 - 29.3）。27%的患者出现3/4级毒性反应，12%的患者需要调整帕唑帕尼剂量，21%的患者因毒性反应需要永久停药。
我们的研究表明，帕唑帕尼在STS罕见亚型中具有活性。
