The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Eur Urol Oncol. 2023 Jun;6(3):339-348. doi: 10.1016/j.euo.2023.01.012. Epub 2023 Feb 25.
BACKGROUND: The comparative efficacy and health-related quality of life (HRQoL) outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib as first-line treatments for advanced renal cell carcinoma (aRCC) have not been assessed in head-to-head trials. OBJECTIVE: To assess the efficacy and HRQoL outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib. DESIGN, SETTING, AND PARTICIPANTS: Patient-level data for nivolumab plus cabozantinib from the CheckMate 9ER trial and published data for pembrolizumab plus axitinib from the KEYNOTE-426 trial were used. CheckMate 9ER data were reweighted to match the key baseline characteristics as reported in KEYNOTE-426. INTERVENTION: Nivolumab (240 mg every 2 wk) plus cabozantinib (40 mg once daily) and pembrolizumab (200 mg every 3 wk) plus axitinib (5 mg twice daily, initially). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Hazard ratios (HRs) for progression-free survival (PFS), duration of response, overall survival (OS), and deterioration in HRQoL were assessed using weighted Cox proportional-hazard models, with sunitinib as a common anchor. Objective response rates (ORRs) and changes in HRQoL scores from baseline were assessed as difference-in-differences for the two treatments relative to sunitinib. RESULTS AND LIMITATIONS: After balancing patient characteristics between the trials, nivolumab plus cabozantinib was associated with significantly improved PFS (HR [95% confidence interval {CI}] 0.70 [0.53-0.93]; p = 0.01) and a significantly decreased risk of confirmed deterioration in HRQoL (Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms: HR [95% CI] 0.48 [0.34-0.69]) versus pembrolizumab plus axitinib. OS was similar between treatments (HR [95% CI] 0.99 [0.67-1.44]; p = 0.94). Nivolumab plus cabozantinib was associated with numerically greater ORRs (difference-in-difference [95% CI] 8.4% [-1.7 to 18.4]; p = 0.10) and longer duration of response (HR [95% CI] 0.79 [0.47-1.31]; p = 0.36) than pembrolizumab plus axitinib. Comparative studies using data with a longer duration of follow-up are warranted. CONCLUSIONS: Nivolumab plus cabozantinib significantly improved PFS and HRQoL compared with pembrolizumab plus axitinib as first-line treatment for aRCC. PATIENT SUMMARY: This study was conducted to indirectly compare the results of two immunotherapy-based combinations-nivolumab plus cabozantinib versus pembrolizumab plus axitinib-for patients who have not received any treatment for advanced renal cell carcinoma. Patients who received nivolumab plus cabozantinib had a significant improvement in the length of time without worsening of their disease and in their perceived physical and mental health compared with pembrolizumab plus axitinib; patients remained alive for a similar length of time from the start of either treatment. This analysis further adds to our current knowledge of the relative benefits of these two treatment regimens and will help with physician and patient treatment decisions.
背景：纳武利尤单抗联合卡博替尼与帕博利珠单抗联合阿昔替尼作为晚期肾细胞癌（aRCC）的一线治疗方案，其疗效和健康相关生活质量（HRQoL）结局在头对头试验中尚未得到评估。
目的：评估纳武利尤单抗联合卡博替尼与帕博利珠单抗联合阿昔替尼的疗效和 HRQoL 结局。
设计、地点和参与者：使用 CheckMate 9ER 试验中纳武利尤单抗联合卡博替尼的患者水平数据和 KEYNOTE-426 试验中帕博利珠单抗联合阿昔替尼的已发表数据。CheckMate 9ER 数据经过重新加权，以匹配 KEYNOTE-426 报告的关键基线特征。
干预措施：纳武利尤单抗（每 2 周 240 mg）加卡博替尼（每天 40 mg）和帕博利珠单抗（每 3 周 200 mg）加阿昔替尼（每天 2 次，5 mg，初始剂量）。
结局测量和统计分析：使用加权 Cox 比例风险模型评估无进展生存期（PFS）、缓解持续时间、总生存期（OS）和 HRQoL 恶化的风险比（HR），以舒尼替尼为共同锚点。使用差异法评估相对于舒尼替尼，两种治疗方法的客观缓解率（ORR）和 HRQoL 评分的变化。
结果和局限性：在平衡试验间患者特征后，与帕博利珠单抗联合阿昔替尼相比，纳武利尤单抗联合卡博替尼显著改善了 PFS（HR [95%置信区间 {CI}] 0.70 [0.53-0.93]；p = 0.01）和降低了确认的 HRQoL 恶化风险（功能性评估癌症治疗-肾脏症状指数-疾病相关症状：HR [95%CI] 0.48 [0.34-0.69]）。两种治疗方法的 OS 相似（HR [95%CI] 0.99 [0.67-1.44]；p = 0.94）。与帕博利珠单抗联合阿昔替尼相比，纳武利尤单抗联合卡博替尼的 ORR 更高（差值[95%CI] 8.4%[-1.7 至 18.4]；p = 0.10），缓解持续时间更长（HR [95%CI] 0.79 [0.47-1.31]；p = 0.36）。需要使用具有更长随访时间的数据进行比较研究。
结论：与帕博利珠单抗联合阿昔替尼作为 aRCC 的一线治疗相比，纳武利尤单抗联合卡博替尼可显著改善 PFS 和 HRQoL。
患者总结：本研究旨在间接比较两种免疫治疗联合方案（纳武利尤单抗联合卡博替尼与帕博利珠单抗联合阿昔替尼）在未经任何治疗的晚期肾细胞癌患者中的疗效。与帕博利珠单抗联合阿昔替尼相比，接受纳武利尤单抗联合卡博替尼治疗的患者在疾病无恶化时间和身体及心理健康感知方面有显著改善；从任何一种治疗开始，患者的存活时间相似。这项分析进一步增加了我们对这两种治疗方案相对益处的了解，将有助于医生和患者的治疗决策。
Cochrane Database Syst Rev. 2020-10-14
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