Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma.
Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma.
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Pembrolizumab单药治疗的长期安全性及其与临床结局的关系：晚期黑色素瘤患者的里程碑式分析
DOI：
10.1016/j.ejca.2020.11.010
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Joshua AM
中科院分区：
文献类型：
--
作者：
Robert C;Hwu WJ;Hamid O;Ribas A;Weber JS;Daud AI;Hodi FS;Wolchok JD;Mitchell TC;Hersey P;Dronca R;Joseph RW;Boutros C;Min L;Long GV;Schachter J;Puzanov I;Dummer R;Lin J;Ibrahim N;Diede SJ;Carlino MS;Joshua AM
在KEYNOTE-001、KEYNOTE-002和KEYNOTE-006中分析了派姆单抗在黑色素瘤中的长期安全性。分析涉及接受≥1次帕博利珠单抗给药的患者。在第147天前无进展的患者中，通过里程碑分析解决了提前期偏倚。分析了1567例患者的不良事件（AE）（中位随访时间为42.4个月）。大多数AE为轻度/中度; 17.7%的患者发生3/4级治疗相关AE。发生了2例pembrolizumab相关死亡。23.0%的患者发生任何级别的免疫介导AE（imAE），最常见的是甲状腺功能减退症（9.1%）、肺炎（3.3%）和甲状腺功能亢进症（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imAE（n = 79）与未发生imAE（n = 384）的患者的客观缓解率（ORR）相似（64.6% vs 63.0%）;两组的中位至缓解时间（TTR）均为5.6个月;中位缓解持续时间（DOR）分别为20.0 vs 25.3个月;中位无进展生存期（PFS）为17.0个月与17.7个月;中位总生存期（OS）为未达到（NR）与43个月（p = 0.1104）。接受（n = 17）与未接受（n = 62）全身性皮质类固醇的患者的ORR（70.6% vs. 62.9%）和中位TTR（6.4 vs. 5.6个月）相似，但中位PFS在数值上较短（9.9 vs. 17.0个月）;中位DOR，14.2个月vs. NR;中位OS，两者均为NR。这些结果增强了pembrolizumab在晚期黑色素瘤中的知识基础，在大量人群的长期随访后没有新的毒性信号。在里程碑分析中，无论imAE或全身性皮质类固醇使用情况如何，帕博利珠单抗疗效相似。NCT 01295827、NCT 01704287、NCT 01866319。
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.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
51.1
作者：
Ribas, Antoni;Puzanov, Igor;Dummer, Reinhard;Schadendorf, Dirk;Hamid, Omid;Robert, Caroline;Hodi, F. Stephen;Schachter, Jacob;Pavlick, Anna C.;Lewis, Karl D.;Cranmer, Lee D.;Blank, Christian U.;O'Day, Steven J.;Ascierto, Paolo A.;Salama, April K. S.;Margolin, Kim A.;Loquai, Carmen;Eigentler, Thomas K.;Gangadhar, Tara C.;Carlino, Matteo S.;Agarwala, Sanjiv S.;Moschos, Stergios J.;Sosman, Jeffrey A.;Goldinger, Simone M.;Shapira-Frommer, Ronnie;Gonzalez, Rene;Kirkwood, John M.;Wolchok, Jedd D.;Eggermont, Alexander;Li, Xiaoyun Nicole;Zhou, Wei;Zernhelt, Adriane M.;Lis, Joy;Ebbinghaus, Scot;Kang, S. Peter;Daud, Adil
通讯作者：
Daud, Adil
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni
影响因子：
45.3
作者：
Weber, Jeffrey S.;Hodi, F. Stephen;Robert, Caroline
通讯作者：
Robert, Caroline
DOI：
10.2147/ccid.s120877
发表时间：
2017
期刊：
Clinical, cosmetic and investigational dermatology
影响因子：
--
作者：
Karlsson AK;Saleh SN
通讯作者：
Saleh SN