Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, London; Royal Free National Health Service Trust, London, UK.
Bradford Hill Clinical Research Center, Santiago, Chile.
ESMO Open. 2024 May;9(5):102994. doi: 10.1016/j.esmoop.2024.102994. Epub 2024 Apr 20.
Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18.1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score.
Patients with treatment-naïve aRCC received NIVO 240 mg every 2 weeks plus CABO 40 mg once daily or SUN 50 mg for 4 weeks (6-week cycles), until disease progression/unacceptable toxicity (maximum NIVO treatment, 2 years). Primary endpoint was progression-free survival (PFS) per blinded independent central review (BICR). Secondary endpoints were overall survival (OS), objective response rate (ORR) per BICR, and safety and tolerability.
Overall, 323 patients were randomised to NIVO + CABO and 328 to SUN. Median PFS was improved with NIVO + CABO versus SUN [16.6 versus 8.4 months; hazard ratio (HR) 0.59; 95% confidence interval (CI) 0.49-0.71]; median OS favoured NIVO + CABO versus SUN (49.5 versus 35.5 months; HR 0.70; 95% CI 0.56-0.87). ORR (95% CI) was higher with NIVO + CABO versus SUN [56% (50% to 62%) versus 28% (23% to 33%)]; 13% versus 5% of patients achieved complete response, and median duration of response was 22.1 months versus 16.1 months, respectively. PFS and OS favoured NIVO + CABO over SUN across intermediate, poor and intermediate/poor IMDC risk subgroups; higher ORR and complete response rates were seen with NIVO + CABO versus SUN regardless of IMDC risk subgroup. Any-grade (grade ≥3) treatment-related adverse events occurred in 97% (67%) versus 93% (55%) of patients treated with NIVO + CABO versus SUN.
After extended follow-up, NIVO + CABO maintained survival and response benefits; safety remained consistent with previous follow-ups. These results continue to support NIVO + CABO as a first-line treatment for aRCC.
ClinicalTrials.gov, NCT03141177.
纳武利尤单抗联合卡博替尼（NIVO+CABO）基于 III 期 CheckMate 9ER 试验（数据库锁定日期时的中位随访生存期为 18.1 个月）中与舒尼替尼（SUN）相比的优越性，被批准用于晚期肾细胞癌（aRCC）的一线治疗；在中位随访生存期扩展至 32.9 个月时，仍保持疗效获益。我们报告了意向治疗（ITT）患者在中位生存期随访 44.0 个月后的更新疗效和安全性数据，以及包括国际转移性肾细胞癌数据库联盟（IMDC）预后风险评分在内的额外亚组分析结果。
未经治疗的 aRCC 患者接受纳武利尤单抗 240 mg 每 2 周一次联合卡博替尼 40 mg 每日一次或舒尼替尼 50 mg 每周 4 周（6 周周期），直至疾病进展/无法耐受毒性（纳武利尤单抗治疗最长 2 年）。主要终点是盲法独立中央审查（BICR）评估的无进展生存期（PFS）。次要终点是总生存期（OS）、BICR 评估的客观缓解率（ORR）以及安全性和耐受性。
总体而言，323 例患者随机分配至 NIVO+CABO 组，328 例患者随机分配至 SUN 组。与 SUN 相比，NIVO+CABO 组的中位 PFS 得到改善[16.6 个月与 8.4 个月；风险比（HR）0.59；95%置信区间（CI）0.49-0.71]；NIVO+CABO 组的中位 OS 优于 SUN 组[49.5 个月与 35.5 个月；HR 0.70；95%CI 0.56-0.87]。与 SUN 相比，NIVO+CABO 组的 ORR（95%CI）更高[56%（50%至 62%）与 28%（23%至 33%）]；分别有 13%和 5%的患者达到完全缓解，中位缓解持续时间分别为 22.1 个月和 16.1 个月。在中间、不良和中间/不良 IMDC 风险亚组中，NIVO+CABO 组的 PFS 和 OS 均优于 SUN 组；无论 IMDC 风险亚组如何，NIVO+CABO 组的 ORR 和完全缓解率均更高。接受 NIVO+CABO 治疗的患者中有 97%（67%）发生任何级别（≥3 级）治疗相关不良事件，而接受 SUN 治疗的患者中有 93%（55%）发生该事件。
在延长随访后，NIVO+CABO 保持了生存和缓解获益；安全性与之前的随访结果一致。这些结果继续支持 NIVO+CABO 作为 aRCC 的一线治疗药物。
ClinicalTrials.gov，NCT03141177。
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