Mark Michael, Mora Alfonso Rojas, Winder Thomas, Stathis Anastasios, Jakob Andreas, Müller Gisela, Hayoz Stefanie, Reimann Patrick, Petrausch Ulf, von Moos Roger
Division of Oncology/Hematology, Cantonal Hospital Graubuenden, Chur, Switzerland.
Università della Svizzera italiana, Faculty of Biomedical Sciences, Lugano, Switzerland.
Bone Rep. 2024 Jul 23;22:101794. doi: 10.1016/j.bonr.2024.101794. eCollection 2024 Sep.
Patients with bone metastases from solid tumors often have additional treatment with bone targeted agents (BTAs) to avoid symptomatic skeletal events (SSEs) such as clinically significant pathological fracture leading toradiation therapy or surgery to the bone, spinal cord compression, or hypercalcemia. The absolute value of BTA treatment in the era of immunotherapy (IO) is unknown.
Patients with bone metastases treated with immunotherapy within the Alpine Tumor Immunology Registry were compared based on whether they received an additional BTA such as denosumab or zoledronic acid. The primary endpoint was time to first SSE. Continuous data were summarized as median and range, categorical data using frequency counts and percentages. Kaplan-Meier estimates were used to describe and visualize the effect of categorical variables.
One hundred and ninety-seven patients with bone metastases and treatment with immunotherapy such as nivolumab (48 %), pembrolizumab (40 %), atezolizumab (12 %), ipilimumab (9 %) and other immunotherapy (5 %) were included. The most frequent tumor types were lung cancer (50 %), malignant melanoma (11 %), renal cell cancer (10 %) and bladder cancer (9 %), respectively. One hundred and twenty-two patients (62 %) received a BTA treatment (91 % denosumab). The median treatment duration of a BTA was 178 days (min: 1 day, max: 2010 days). Out of the 197 patients, 47 (24 %) experienced at least one SSE, 100 (51 %) had bone pain. Ten of the 122 patients (8 %) receiving a BTA developed osteonecrosis of the jaw (ONJ). The percentage of patients without an SSE at fixed time points was higher if treated with a BTA (e.g., at 6 months, 92 % [95 % CI: 84 % - 96 %] versus 88 % [95 % CI: 77 % - 94 %]), but no significant difference in time to first SSE (HR 0.69; 95 % CI 0.34-1.39, log-rank = 0.29) or time to first bone pain (HR: 0.85; 95 % CI: 0.51-1.43, = 0.54) between these two groups could be detected. There were differences in OS between patients treated with a BTA and patients not treated with a BTA (HR: 1.46; 95 % CI: 1.01-2.10, = 0.043).
No significant difference in time to first SSE or bone pain was observed between patients who have received a BTA or not when treated with immunotherapy. Based on these retrospective results the indication of BTAs to reduce SSEs in cancer patients under treatment with immunotherapy needs further evaluation.
实体瘤骨转移患者常接受骨靶向药物（BTA）的额外治疗，以避免出现有症状的骨骼事件（SSE），如导致骨放疗或手术、脊髓压迫或高钙血症的具有临床意义的病理性骨折。在免疫治疗（IO）时代，BTA治疗的绝对值尚不清楚。
在阿尔卑斯肿瘤免疫登记处接受免疫治疗的骨转移患者，根据是否接受了如地诺单抗或唑来膦酸等额外的BTA进行比较。主要终点是首次发生SSE的时间。连续数据总结为中位数和范围，分类数据使用频数和百分比。采用Kaplan-Meier估计来描述和可视化分类变量的影响。
纳入了197例骨转移且接受免疫治疗的患者，如纳武利尤单抗（48%）、帕博利珠单抗（40%）、阿替利珠单抗（12%）、伊匹木单抗（9%）和其他免疫治疗（5%）。最常见的肿瘤类型分别为肺癌（50%）、恶性黑色素瘤（11%）、肾细胞癌（10%）和膀胱癌（9%）。122例患者（62%）接受了BTA治疗（91%为地诺单抗）。BTA的中位治疗持续时间为178天（最小值：1天，最大值：2010天）。在197例患者中，47例（24%）经历了至少一次SSE，100例（51%）有骨痛。122例接受BTA治疗的患者中有10例（8%）发生了颌骨坏死（ONJ）。接受BTA治疗的患者在固定时间点无SSE的百分比更高（例如，在6个月时，92%[95%CI：84%-96%]对88%[95%CI：77%-94%]），但两组之间首次发生SSE的时间（HR 0.69；95%CI 0.34-1.39，对数秩检验=0.29）或首次出现骨痛的时间（HR：0.85；95%CI：0.51-1.43，=0.54）无显著差异。接受BTA治疗的患者与未接受BTA治疗的患者的总生存期存在差异（HR：1.46；95%CI：1.01-2.10，=0.043）。
接受免疫治疗的患者中，接受或未接受BTA治疗的患者在首次发生SSE或骨痛的时间上无显著差异。基于这些回顾性结果，在接受免疫治疗的癌症患者中使用BTA来减少SSE的适应证需要进一步评估。
