背景:卡利珠单抗联合阿帕替尼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,并探索潜在的生存生物标志物。还报告了接受免疫检查点抑制剂(ICI)再治疗的患者的结果。
方法:在这项II期试验中,符合条件的患者每2周静脉注射卡利珠单抗200mg,每日一次阿帕替尼250mg,共4周,为期2年.继续治疗直到疾病进展,不可接受的毒性,或撤回同意。
结果:2019年1月21日至8月1日,共纳入45例患者。截至2023年7月31日的数据分析,代表所有患者治疗开始后超过48个月。9名(20.0%)患者完成了为期2年的研究。中位反应持续时间(DOR)为16.6个月,45.0%的患者DOR≥24个月。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%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OS率为47.8%(95%CI,31.7-62.3)。年龄>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(vs.<1),高肿瘤突变负担,PIK3CA突变与改善的PFS(风险比[HR]<1)和较长的OS(HR<1)相关。最初在CLAP试验中反应但后来经历疾病进展的八名患者接受ICI治疗。其中,2(25.0%)获得了部分响应,5例(62.5%)病情稳定。值得注意的是,4例接受ICIs再治疗的患者存活超过45个月.在本研究中没有发现新的安全性信号。
结论:长期生存随访数据表明,卡利珠单抗联合阿帕替尼具有稳健的,持续,以及在一线铂类化疗后进展的晚期宫颈癌患者的持久疗效。长期治疗没有发现新的安全信号。
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.
CONCLUSIONS: 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.