Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Dermatology, Niigata Cancer Center Hospital, Niigata, Japan.
J Dermatol. 2024 May;51(5):632-642. doi: 10.1111/1346-8138.17002. Epub 2024 Mar 26.
Pembrolizumab demonstrated an acceptable safety profile and promising antitumor activity in Japanese patients with advanced melanoma in the phase 1b KEYNOTE-041 (Study of Pembrolizumab [MK-3475] in Participants With Advanced Melanoma) trial. To evaluate the long-term efficacy and safety of pembrolizumab in Japanese patients with advanced melanoma in KEYNOTE-041. The current analysis reports results of additional follow-up of approximately 12 months since the initial analysis. Eligible patients had locally advanced (unresectable stage III) or metastatic (stage IV) melanoma not amenable to local therapy and had received two or fewer prior systemic therapies. Pembrolizumab 2 mg/kg was given every 3 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points included safety, tolerability, and overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by independent central review. The data cutoff for this analysis was August 30, 2017. Forty-two patients were followed up for a median of 22.3 months (range, 2.63-30.82 months). The ORR was 24.3% (nine of 37 evaluable patients [95% confidence interval (CI), 11.8%-41.2%]). Two patients with partial response at the time of the initial analysis achieved complete response. The median overall survival (OS) was 25.1 months (95% CI, 13.1-not reached] and the 30-month OS rate was 46.3% (95% CI, 29.8%-61.3%). The median duration of response was not reached. Treatment-related adverse events (TRAEs) were reported in 78.6% of patients; the incidence of grade 3 to 5 TRAEs was 23.8%. No additional treatment-related deaths occurred since the initial analysis. Pembrolizumab provided durable antitumor activity and an acceptable safety profile in Japanese patients with advanced melanoma.
帕博利珠单抗在 KEYNOTE-041 研究(帕博利珠单抗[MK-3475]在晚期黑色素瘤参与者中的研究)中,显示出可接受的安全性概况和有前景的抗肿瘤活性,该研究纳入了日本晚期黑色素瘤患者。为了评估帕博利珠单抗在 KEYNOTE-041 日本晚期黑色素瘤患者中的长期疗效和安全性。本分析报告了初始分析后约 12 个月的额外随访结果。符合条件的患者患有局部晚期(不可切除的 III 期)或转移性(IV 期)黑色素瘤,不适宜局部治疗,且接受过两次或两次以下的系统治疗。帕博利珠单抗 2mg/kg,每 3 周给药,最多 2 年,或直至确认疾病进展或不可接受的毒性。主要终点包括安全性、耐受性和独立中心审查的实体瘤反应评价标准 1.1 版的总缓解率(ORR)。本次分析的数据截止日期为 2017 年 8 月 30 日。42 例患者的中位随访时间为 22.3 个月(范围:2.63-30.82 个月)。ORR 为 24.3%(37 例可评估患者中的 9 例[95%置信区间(CI):11.8%-41.2%])。初始分析时,两名部分缓解的患者获得完全缓解。中位总生存期(OS)为 25.1 个月(95%CI:13.1-未达到],30 个月 OS 率为 46.3%(95%CI:29.8%-61.3%)。中位缓解持续时间未达到。78.6%的患者报告了治疗相关不良事件(TRAEs);3 级至 5 级 TRAEs 的发生率为 23.8%。自初始分析以来,未发生其他治疗相关死亡事件。帕博利珠单抗为日本晚期黑色素瘤患者提供了持久的抗肿瘤活性和可接受的安全性概况。