Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Oncology Department, Bradford Hill Clinical Research Center, Santiago, Chile.
Clin Drug Investig. 2022 Jul;42(7):611-622. doi: 10.1007/s40261-022-01170-6. Epub 2022 Jun 13.
Novel immunotherapy-based combination treatments have drastically improved clinical outcomes for previously untreated patients with advanced/metastatic renal cell carcinoma (aRCC). This study aimed to assess the temporal trends in grade 3/4 adverse event (AE) rates and associated costs of nivolumab plus cabozantinib combination therapy versus sunitinib monotherapy in previously untreated patients with aRCC.
Individual patient data from the CheckMate 9ER trial (nivolumab plus cabozantinib: N = 320; sunitinib: N = 320) were used to calculate the proportion of patients experiencing grade 3/4 AEs. AE unit costs were obtained from the United States (US) 2017 Healthcare Cost and Utilization Project (HCUP) and inflated to 2020 US dollars. Per-patient-per-month (PPPM) all-cause and treatment-related grade 3/4 AE costs over 18-months, temporal trends, and top drivers of AE costs were evaluated in both treatment arms.
Overall, the proportion of patients experiencing grade 3/4 AEs decreased over time, with the highest rates observed in the first 3 months for the nivolumab plus cabozantinib and sunitinib arms. Compared with sunitinib, nivolumab plus cabozantinib was associated with consistently lower average all-cause AE costs PPPM [month 3: $2021 vs. $3097 (p < 0.05); month 6: $1653 vs. $2418 (p < 0.05); month 12: $1450 vs. $1935 (p > 0.05); month 18: $1337 vs. $1755 (p > 0.05)]. Over 18 months, metabolism and nutrition disorders ($244), laboratory abnormalities ($182), and general disorders and administration site conditions ($122) were the costliest all-cause PPPM AE categories in the nivolumab plus cabozantinib arm, and laboratory abnormalities ($443), blood and lymphatic system disorders ($254), and metabolism and nutrition disorders ($177) were the costliest in the sunitinib arm. Trends of treatment-related AE costs were consistent with all-cause AE costs.
Nivolumab plus cabozantinib was associated with lower costs of grade 3/4 AE management PPPM than sunitinib, which accumulated over the 18-month study period.
新型免疫疗法为以前未经治疗的晚期/转移性肾细胞癌（aRCC）患者带来了显著改善的临床结果。本研究旨在评估纳武利尤单抗联合卡博替尼与舒尼替尼单药治疗以前未经治疗的 aRCC 患者的 3/4 级不良事件（AE）发生率和相关成本的时间趋势。
使用 CheckMate 9ER 试验的个体患者数据（纳武利尤单抗联合卡博替尼：N=320；舒尼替尼：N=320）计算发生 3/4 级 AE 的患者比例。AE 单位成本从美国（US）2017 年医疗保健成本和利用项目（HCUP）中获得，并换算为 2020 年美元。在两个治疗组中，评估了 18 个月内每患者每月（PPPM）所有原因和治疗相关的 3/4 级 AE 成本、时间趋势和 AE 成本的主要驱动因素。
总体而言，发生 3/4 级 AE 的患者比例随时间降低，纳武利尤单抗联合卡博替尼和舒尼替尼组在头 3 个月观察到的发生率最高。与舒尼替尼相比，纳武利尤单抗联合卡博替尼的平均全因 AE 成本 PPPM 始终较低[第 3 个月：$2021 与$3097（p<0.05）；第 6 个月：$1653 与$2418（p<0.05）；第 12 个月：$1450 与$1935（p>0.05）；第 18 个月：$1337 与$1755（p>0.05）]。在 18 个月期间，代谢和营养障碍（$244）、实验室异常（$182）和一般疾病和管理部位情况（$122）是纳武利尤单抗联合卡博替尼组中全因 PPPM AE 类别中最昂贵的，而实验室异常（$443）、血液和淋巴系统障碍（$254）和代谢和营养障碍（$177）是舒尼替尼组中最昂贵的。治疗相关 AE 成本的趋势与全因 AE 成本一致。
纳武利尤单抗联合卡博替尼与舒尼替尼相比，在 18 个月的研究期间，每患者每月管理 3/4 级 AE 的成本较低。
