PDF(Pubmed)
Abstract：
Survival is generally poor for Chinese patients with advanced melanoma because of high rates of acral and mucosal melanoma and limited therapeutic options. The first analysis of the phase 1b KEYNOTE-151 study showed second-line pembrolizumab was well tolerated and had clinically meaningful antitumor activity in Chinese patients with advanced melanoma. Three-year follow-up is presented. Eligible patients were of Chinese descent and had unresectable stage III/IV melanoma that progressed after first-line therapy. Patients received pembrolizumab 2 mg/kg every 3 weeks for ≤35 cycles. Primary end points were safety and objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Response was assessed per RECIST v1.1 by blinded independent central review. Subgroup analyses were conducted by melanoma subtype and BRAF and PD-L1 status (acral melanoma only). 103 patients were enrolled; median follow-up duration (time from first dose to data cutoff [July 13, 2020]) was 44.6 months (IQR, 39.1-46.2). Any-grade treatment-related adverse events (TRAEs) occurred in 85.4% of patients, and grade 3/4 TRAEs in 12.6%. No grade 5 TRAEs occurred. Three patients discontinued pembrolizumab because of TRAEs (immune-mediated hepatitis, pneumonia, and arthritis). Immune-mediated AEs and infusion reactions occurred in 34.0% (grade 3/4, 2.9%). ORR was 17.6% (95% CI, 10.8-26.4; 1 complete response/17 partial responses), and median DOR was 13.8 months (range, 2.7-37.4+). Median PFS was 2.8 months (95% CI, 2.7-3.5) and 36-month PFS rate was 5.0%. Median OS was 13.2 months (95% CI, 10.4-16.5) and 36-month OS rate was 22.3%. Median OS for patients with known melanoma subtype was 14.8 months for acral, 13.5 months for nonacral cutaneous, and 7.4 months for mucosal melanoma. Among the acral subgroup, median OS was 22.8 months for PD-L1-positive disease, 8.4 months for PD-L1-negative disease, 18.5 months for BRAF wild-type disease, and 5.8 months for BRAF-mutant disease. Over 3 years\' follow-up, second-line pembrolizumab continued to show manageable safety, clinically meaningful antitumor activity, and durable responses in Chinese patients with advanced melanoma. Subgroup analysis suggested particular benefit in PD-L1-positive and BRAF wild-type acral melanoma, although small subgroup sizes preclude definitive conclusions.
https://clinicaltrials.gov, identifier NCT02821000.
https://clinicaltrials.gov, identifier NCT02821000.
摘要：
中国晚期黑色素瘤患者的生存率通常较差，因为肢端和粘膜黑色素瘤的发生率很高，治疗选择有限。1b期KEYNOTE-151研究的首次分析显示，二线pembrolizumab在中国晚期黑色素瘤患者中具有良好的耐受性和临床意义的抗肿瘤活性。提出了三年的后续行动。符合条件的患者为中国血统，患有不可切除的III/IV期黑色素瘤，在一线治疗后进展。患者每3周接受一次pembrolizumab2mg/kg，≤35个周期。主要终点是安全性和客观缓解率（ORR）。次要终点包括缓解持续时间(DOR),无进展生存期（PFS），总生存率（OS）。根据RECISTv1.1通过盲法独立中央审查评估反应。亚组分析通过黑素瘤亚型和BRAF和PD-L1状态(仅肢端黑素瘤)进行。纳入103例患者；中位随访时间（从第一次给药到数据截止[2020年7月13日]的时间）为44.6个月（IQR，39.1-46.2).85.4%的患者发生任何级别的治疗相关不良事件（TRAEs），3/4级TRAEs占12.6%。没有发生5级TRAE。三名患者因TRAE（免疫介导性肝炎，肺炎,和关节炎）。免疫介导的AE和输注反应发生在34.0%(3/4级,2.9%)。ORR为17.6%（95%CI，10.8-26.4；1个完全缓解/17个部分缓解），中位DOR为13.8个月(范围，2.7-37.4+)。中位PFS为2.8个月（95%CI，2.7-3.5），36个月PFS率为5.0%。中位OS为13.2个月（95%CI，10.4-16.5），36个月OS率为22.3%。已知黑色素瘤亚型患者的中位OS为14.8个月，13.5个月的非肢端皮肤，粘膜黑色素瘤为7.4个月。在肢端亚组中，PD-L1阳性疾病的中位OS为22.8个月，PD-L1阴性疾病8.4个月，BRAF野生型疾病18.5个月，和5.8个月的BRAF突变疾病。超过3年的随访，二线pembrolizumab继续显示出可控的安全性，具有临床意义的抗肿瘤活性，中国晚期黑色素瘤患者的持续反应。亚组分析提示PD-L1阳性和BRAF野生型肢端黑色素瘤有特殊益处,虽然小亚组规模排除了明确的结论。
https://clinicaltrials.gov,标识符NCT02821000。
https://clinicaltrials.gov,标识符NCT02821000。
