Georgetown-Lombardi Comprehensive Cancer Center, 3800 Reservoir Road, NW, Washington DC, 20057, USA.
Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA.
Eur J Cancer. 2021 Mar;145:1-10. doi: 10.1016/j.ejca.2020.12.009. Epub 2021 Jan 4.
Axitinib plus pembrolizumab showed superior overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) versus sunitinib in a randomised phase III trial in patients with advanced renal-cell carcinoma (RCC). We report long-term efficacy and safety of the axitinib/pembrolizumab from the phase I trial (NCT02133742), after 46-55 months from study initiation (data cut-off date, 23rd July 2019).
Fifty-two treatment-naïve patients with advanced RCC were treated with oral axitinib 5 mg twice daily and intravenous pembrolizumab 2 mg/kg every 3 weeks. PFS, duration of response (DoR) and OS were summarised using the Kaplan-Meier method.
At a median follow-up of 42.7 months (95% confidence interval [CI]: 41.1-44.1), median OS was not reached; 38 (73.1%) patients were alive. The probability of being alive at 4 years was 66.8% (95% CI: 49.1-79.5). Median PFS in the overall population was 23.5 months (95% CI: 15.4-30.4). ORR was 73.1%; five patients had complete response. Median DoR was 22.1 months (95% CI: 15.1-34.5). Grade III/IV adverse events (AEs) were reported in 38 (73.1%) patients and 20 (38.5%) discontinued treatment because of AEs: 17 (32.7%) discontinued axitinib, 13 (25.0%) discontinued pembrolizumab, and 10 (19.2%) discontinued both drugs. Common AEs included diarrhoea (84.6%), fatigue (80.8%), hypertension (53.8%), cough (48.1%) and dysphonia (48.1%). There were no new AE terms reported and no treatment-related deaths.
In patients with advanced RCC with ~4 years of follow-up, combination axitinib/pembrolizumab continued to demonstrate clinical benefit, with no new safety signals.
在一项针对晚期肾细胞癌（RCC）患者的随机 III 期试验中，阿昔替尼联合帕博利珠单抗相较于舒尼替尼在总生存期（OS）、无进展生存期（PFS）和客观缓解率（ORR）方面表现出优越性。我们报告了来自 I 期试验（NCT02133742）的阿昔替尼/帕博利珠单抗的长期疗效和安全性，研究起始后 46-55 个月（数据截止日期为 2019 年 7 月 23 日）。
52 名未经治疗的晚期 RCC 患者接受口服阿昔替尼 5mg，每日 2 次，静脉注射帕博利珠单抗 2mg/kg，每 3 周 1 次。使用 Kaplan-Meier 法总结 PFS、缓解持续时间（DoR）和 OS。
中位随访 42.7 个月（95%置信区间：41.1-44.1）时，中位 OS 尚未达到，38（73.1%）名患者存活。4 年时的生存率为 66.8%（95%置信区间：49.1-79.5）。全人群的中位 PFS 为 23.5 个月（95%置信区间：15.4-30.4）。ORR 为 73.1%，5 名患者达到完全缓解。中位 DoR 为 22.1 个月（95%置信区间：15.1-34.5）。38（73.1%）名患者报告了 3 级/4 级不良事件（AE），20（38.5%）名患者因 AE 停止治疗：17（32.7%）名患者停止使用阿昔替尼，13（25.0%）名患者停止使用帕博利珠单抗，10（19.2%）名患者停止使用两种药物。常见的 AE 包括腹泻（84.6%）、疲劳（80.8%）、高血压（53.8%）、咳嗽（48.1%）和声音嘶哑（48.1%）。没有报告新的 AE 术语，也没有治疗相关的死亡。
在晚期 RCC 患者中，中位随访约 4 年，阿昔替尼联合帕博利珠单抗继续显示出临床获益，没有新的安全性信号。
