Long-term survival outcomes and immune checkpoint inhibitor retreatment in patients with advanced cervical cancer treated with camrelizumab plus apatinib in the phase II CLAP study

IF 20.1 1区医学 Q1 ONCOLOGY Cancer Communications Pub Date : 2024-05-13 DOI:10.1002/cac2.12547

Chunyan Lan, Huaiwu Lu, Lin Zhou, Kunlun Liao, Junxiu Liu, Zhiwen Xie, Haixi Liang, Guorong Zou, Ting Yang, Qin Xu, Xin Huang

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Abstract

Background

Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer (CLAP study; NCT03816553). We herein present the updated long-term results of the CLAP study and explore potential biomarkers for survival. The outcomes of patients who underwent immune checkpoint inhibitor (ICI) retreatment were also reported.

Methods

In this phase II trial, eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4-week cycles for up to two years. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent.

Results

Between January 21 and August 1, 2019, a total of 45 patients were enrolled. Data were analyzed as of July 31, 2023, representing > 48 months since treatment initiation for all patients. Nine (20.0%) patients completed the 2-year study. The median duration of response (DOR) was 16.6 months, and 45.0% of patients achieved a DOR of ≥ 24 months. The 12-month progression-free survival (PFS) rate was 40.7% (95% confidence interval [CI], 25.2-55.6), with an 18-month PFS rate of 37.8% (95% CI, 22.7-52.8). The median overall survival (OS) was 20.3 months (95% CI, 9.3-36.9), and the 24-month OS rate was 47.8% (95% CI, 31.7-62.3). Age > 50 years, programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (versus [vs.] < 1), CPS ≥ 10 (vs. < 1), high tumor mutational burden, and PIK3CA mutations were associated with improved PFS (hazard ratio [HR] < 1) and longer OS (HR < 1). Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with ICIs. Among them, 2 (25.0%) achieved a partial response, while 5 (62.5%) had stable disease. Notably, four patients who received retreatment with ICIs survived for more than 45 months. No new safety signals were identified in the present study.

Conclusion

Long-term survival follow-up data demonstrated that camrelizumab plus apatinib has robust, sustained, and durable efficacy in patients with advanced cervical cancer who progress after first-line platinum-based chemotherapy. No new safety signals were noted with long-term treatment.

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在 CLAP II 期研究中，接受坎瑞珠单抗加阿帕替尼治疗的晚期宫颈癌患者的长期生存结果和免疫检查点抑制剂再治疗情况。

研究背景康瑞珠单抗联合阿帕替尼已在晚期宫颈癌患者中显示出强大的抗肿瘤活性和安全性（CLAP 研究；NCT03816553）。我们在此介绍 CLAP 研究的最新长期结果，并探讨潜在的生存生物标志物。同时还报告了接受免疫检查点抑制剂（ICI）再治疗的患者的结果：在这项II期试验中，符合条件的患者每两周静脉注射一次康瑞珠单抗（camrelizumab）200毫克，同时口服阿帕替尼250毫克，每天一次，4周为一个周期，疗程最长为两年。治疗一直持续到疾病进展、出现不可接受的毒性或撤回同意为止：2019年1月21日至8月1日期间，共有45名患者入组。对截至 2023 年 7 月 31 日的数据进行了分析，所有患者的治疗时间均大于 48 个月。9名患者（20.0%）完成了为期2年的研究。中位应答持续时间（DOR）为16.6个月，45.0%的患者达到了≥24个月的DOR。12个月无进展生存期（PFS）率为40.7%（95%置信区间[CI]，25.2-55.6），18个月PFS率为37.8%（95%置信区间[CI]，22.7-52.8）。中位总生存期（OS）为20.3个月（95% CI，9.3-36.9），24个月的OS率为47.8%（95% CI，31.7-62.3）。年龄大于50岁、程序性死亡配体1（PD-L1）联合阳性评分（CPS）≥1（与[vs.]<1）、CPS≥10（与[vs.]<1）、高肿瘤突变负荷和PIK3CA突变与PFS改善（危险比[HR]<1）和OS延长（HR<1）相关。在CLAP试验中，有8名患者起初有反应，但后来出现了疾病进展，他们接受了ICIs治疗。其中，2 人（25.0%）获得部分应答，5 人（62.5%）病情稳定。值得注意的是，4 名接受 ICIs 治疗的患者存活时间超过 45 个月。本研究未发现新的安全信号：长期生存随访数据表明，康瑞珠单抗联合阿帕替尼对一线铂类化疗后病情进展的晚期宫颈癌患者具有稳健、持续和持久的疗效。长期治疗未发现新的安全性信号。

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来源期刊

Cancer Communications Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

25.50

自引率

4.30%

发文量

153

审稿时长

4 weeks

期刊介绍： Cancer Communications is an open access, peer-reviewed online journal that encompasses basic, clinical, and translational cancer research. The journal welcomes submissions concerning clinical trials, epidemiology, molecular and cellular biology, and genetics.