Department of Oncology, Service of Dermatology, Institut de Cancérologie Gustave Roussy, 114 Rue Edouard Vaillant, Gustave Roussy, Villejuif, 94805, France; Paris-Saclay University, CNRS UMR 3348, Orsay, France.
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
Eur J Cancer. 2021 Feb;144:182-191. doi: 10.1016/j.ejca.2020.11.010. Epub 2020 Dec 24.
Long-term safety of pembrolizumab in melanoma was analyzed in KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006.
Analysis involved patients who received ≥1 pembrolizumab dose. Lead-time bias was addressed via landmark analyses in patients who were progression-free before day 147.
Adverse events (AEs) were analyzed for 1567 patients (median follow-up, 42.4 months). Most AEs were mild/moderate; grade 3/4 treatment-related AEs occurred in 17.7% of patients. Two pembrolizumab-related deaths occurred. Any-grade immune-mediated AEs (imAEs) occurred in 23.0%, most commonly hypothyroidism (9.1%), pneumonitis (3.3%), and hyperthyroidism (3.0%); grade 3/4 imAEs occurred in 6.9% of patients. Most imAEs occurred within 16 weeks of treatment. In landmark analysis, patients who did (n = 79) versus did not (n = 384) develop imAEs had similar objective response rates (ORRs) (64.6% versus 63.0%); median time to response (TTR), 5.6 months for both; median duration of response (DOR), 20.0 versus 25.3 months; median progression-free survival (PFS), 17.0 versus 17.7 months; median overall survival (OS), not reached (NR) versus 43 months (p = 0.1104). Patients who did (n = 17) versus did not (n = 62) receive systemic corticosteroids had similar ORRs (70.6% vs. 62.9%) and median TTR (6.4 vs. 5.6 months) but numerically shorter median PFS (9.9 vs. 17.0 months); median DOR, 14.2 months versus NR; median OS, NR for both.
These results enhance the knowledge base for pembrolizumab in advanced melanoma, with no new toxicity signals after lengthy follow-up of a large population. In landmark analyses, pembrolizumab efficacy was similar regardless of imAEs or systemic corticosteroid use.
NCT01295827, NCT01704287, NCT01866319.
对 KEYNOTE-001、KEYNOTE-002 和 KEYNOTE-006 中的 pembrolizumab 在黑色素瘤中的长期安全性进行分析。
分析纳入了接受至少 1 剂 pembrolizumab 的患者。通过对第 147 天前无进展的患者进行里程碑分析，解决了领先时间偏倚问题。
对 1567 例患者（中位随访时间 42.4 个月）进行了不良事件（AE）分析。大多数 AE 为轻度/中度；17.7%的患者出现 3/4 级治疗相关 AE。2 例 pembrolizumab 相关死亡事件发生。23.0%的患者发生任何级别免疫介导的 AE（imAE），最常见的是甲状腺功能减退（9.1%）、肺炎（3.3%）和甲状腺功能亢进（3.0%）；6.9%的患者发生 3/4 级 imAE。大多数 imAE 发生在治疗后 16 周内。在里程碑分析中，发生（n=79）与未发生（n=384）imAE 的患者客观缓解率（ORR）相似（64.6% vs. 63.0%）；中位反应时间（TTR）均为 5.6 个月；中位缓解持续时间（DOR）分别为 20.0 个月和 25.3 个月；中位无进展生存期（PFS）分别为 17.0 个月和 17.7 个月；中位总生存期（OS）均未达到（NR）和 43 个月（p=0.1104）。发生（n=17）与未发生（n=62）系统性皮质类固醇治疗的患者 ORR 相似（70.6% vs. 62.9%），TTR 中位数（6.4 个月 vs. 5.6 个月）也相似，但 PFS 中位数（9.9 个月 vs. 17.0 个月）较短；DOR 中位数分别为 14.2 个月和 NR；OS 中位数均未达到。
这些结果增强了对晚期黑色素瘤中 pembrolizumab 的认识基础，在对大量人群进行长时间随访后，没有新的毒性信号。在里程碑分析中，无论是否发生 imAE 或使用系统性皮质类固醇，pembrolizumab 的疗效均相似。
NCT01295827、NCT01704287、NCT01866319。
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