Division of Hematology Oncology, Massachusetts General Hospital, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Massachusetts General Hospital Biostatistics Center, Boston, MA, USA.
Oncologist. 2022 Jul 5;27(7):600-606. doi: 10.1093/oncolo/oyac083.
Bone metastases are often difficult to manage as they can be symptomatic and skeletal-related events (SREs) can contribute to significant morbidity and declines in performance status. We sought to identify a novel medical treatment for bone metastasis by testing the safety and efficacy of cabozantinib in patients with bone metastasis arising from non-breast, non-prostate, malignant solid tumors. Patients were administered cabozantinib as an oral drug starting at 60 mg per day and radiologic measurements were performed at baseline and every 8 weeks. Thirty-seven patients were enrolled. No SREs were observed throughout the study. Twenty patients had disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Four of 20 had a partial response by RECIST. An additional 12 patients had some decrease in tumor burden with nine of these having a decrease in tumor burden of at least 10% by RECIST. Six of the patients with at least a minor response had sarcoma. Sixteen patients had biomarkers of bone turnover measured before and after treatment. Most of these patients demonstrated decrease in urine and serum N-telopeptide and serum C-telopeptide. However, these changes in biomarkers of bone turnover did not correlate with radiographic changes measured by RECIST. This study demonstrates clinical activity and safety for cabozantinib in heavily pretreated patients with bone metastasis and shows activity for cabozantinib in patients with metastatic sarcoma.
骨转移通常难以治疗,因为它们可能有症状,骨骼相关事件 (SREs) 可导致显著的发病率和功能状态下降。我们试图通过测试卡博替尼在非乳腺癌、非前列腺、恶性实体瘤骨转移患者中的安全性和疗效来寻找一种新的骨转移治疗方法。患者每天口服卡博替尼 60 毫克起始治疗,在基线和每 8 周进行影像学测量。共纳入 37 例患者。整个研究过程中未观察到 SREs。20 例患者的疾病可通过实体瘤反应评估标准 1.1 版 (RECIST) 进行测量。20 例中有 4 例达到 RECIST 部分缓解。另外 12 例肿瘤负荷有一定程度的减少,其中 9 例肿瘤负荷减少至少 10%。这 6 例有部分缓解的患者均患有肉瘤。16 例患者在治疗前后测量了骨转换生物标志物。这些患者中的大多数表现为尿和血清 N-端肽和血清 C-端肽减少。然而,这些骨转换生物标志物的变化与 RECIST 测量的影像学变化无关。本研究表明卡博替尼在骨转移的大量预处理患者中具有临床活性和安全性,并显示卡博替尼在转移性肉瘤患者中有活性。