pembrolizumab

根据发表在《柳叶刀》杂志上的随机第3期KEYNOTE-048研究的结果，将Pembrolizumab联合铂类化学疗法联合治疗对于复发或转移性头颈部鳞状细胞癌似乎是一种安全有效的一线治疗。 根据安全性和有效性数据，研究人员还认为，用派姆单抗（Keytruda，Merck）进行一线单药治疗适合PD-L1阳性复发或转移性HNSCC患者。  “我相信这项研究的结果已经改变护理标准，” 芭芭拉Burtness医师，医学院和耶鲁大学癌症中心的耶鲁大学医学院教授，HemOnc今天编委，告诉Healio。“ FDA在6月的第一线批准了pembrolizumab，因此，PD-L1表达患者的pembrolizumab单药疗法以及所有患者的pembrolizumab联合化疗现在已成为治疗的标准。” Burtness和同事写道，在HNSCC中将化疗与免疫检查点抑制剂联合使用是有意义的，因为它破坏了肿瘤结构，从而减少了免疫排斥，导致抗原脱落，并促进了疾病的快速控制。 研究人员进行了本试验，以确定在复发性或转移性HNSCC患者中，与EGFR抑制剂西妥昔单抗（Erbitux，Eli Lilly）相比，PD-1抑制剂pembrolizumab单药治疗或联合化疗是否能改善OS。 研究人员将882例先前未接受过治疗的复发或转移性HNSCC患者随机分配为pembrolizumab单药治疗（n = 301），pembrolizumab联合卡铂或顺铂和5-FU（n = 281）或西妥昔单抗联合卡铂或顺铂和5-FU（n = 300）。 在所有患者中，有754名（85％）的PD-L1合并阳性评分（CPS）为1或更高，而381名（43％）的CPS为20或更高。 OS和PFS是研究的主要终点。次要终点包括安全性和耐受性。 pembrolizumab单药治疗组中位随访时间为11.5个月，pembrolizumab化疗组为13个月，西妥昔单抗化疗组为10.7个月。 第二次中期分析的结果显示，在CPS为20或更高的患者（中位14.9个月vs. 10.7个月； HR = 0.61； 95％CI，0.45-0.83）中，单独使用pembrolizumab与西妥昔单抗联合化疗相比改善了OS。 CPS为1或更高（中位数为12.3个月vs. 10.3个月； HR = 0.78； 95％CI，0.64-0.96）。在所有人群中，使用派姆单抗单药治疗的OS均不低于西妥昔单抗和化疗的OS（中位值，分别为11.6个月和10.7个月； HR = 0.85； 95％CI，0.71-1.03）。 研究人员在第二次中期分析中观察到，在所有患者中，使用派姆单抗联合化疗与西妥昔单抗和化疗相比，OS显着改善（中位，13个月vs. 10.7个月； HR = 0.77； 95％CI，0.63-0.93）。他们还报告说，在最终分析中，CPS为20或更高（中位14.7个月vs. 11个月； HR = 0.6； 95％CI，0.45-0.82）和CPS为1或更高的患者在OS方面具有显着的获益。 （13.6个月vs.10.4个月； HR = 0.65； 95％CI，0.53-0.8）。 Read more...

The combination of pembrolizumab plus dabrafenib and trametinib as first-line treatment for BRAF-mutated melanomashowed antitumor activity, but high rates of grade 3-5 treatment-related adverse events, according to results from the phase 2 KEYNOTE-022 trial presented at the ESMO 2018 Congress in Munich, Germany.1 The combination of pembrolizumab plus the BRAF inhibitors dabrafenib and trametinib showed promising antitumor activity in the phase 1 portion of the KEYNOTE-022 trial. This report was of the results from the phase 2 portion. The double-blind, phase 2 KEYNOTE-022 trial randomly assigned 120 patients with treatment-naïve stage III or IV melanoma harboring a BRAFV600E/Kmutation to receive pembrolizumab plus dabrafenib and trametinib or placebo plus dabrafenib and trametinib. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included objective response rate (ORR), duration of response (DoR), time to response, and overall survival (OS). The ORR was 63% with pembrolizumab plus dabrafenib and trametinib compared with 72% with the BRAF inhibitors alone, with complete response rates of 18% and 13%, respectively. The median time to response was similar between arms at 2.8 months. During a median follow-up of 9.6 months, there was a trend toward prolonged PFS with the pembrolizumab combination, but it was not significant based on prespecified parameters that required a hazard ratio (HR) of 0.62 or less. The median PFS with the pembrolizumab combination was 16 months (95% CI, 8.6-21.5 months) compared with 10.3 months (95% CI, 7.0-15.6 months) with dabrafenib plus trametinib alone, resulting in an HR of 0.66 (P = .043). The 12-month PFS was 59% and 45% with the pembrolizumab combination or the BRAF inhibitors alone, respectively. The median DoR was longer with the pembrolizumab combination at 18.7 months (range, 1.9+ to 22.1 months) compared with 12.5 months (range, 2.1-19.5+ months) with dabrafenib plus trametinib. Responses lasting at least 18 months was more common with pembrolizumab, occurring in 60% of patients compared with 28% of patients receiving only the BRAF inhibitors. The 12-month OS was 80% with the pembrolizumab combination compared with 73% with dabrafenib plus trametinib. There were similar rates of any grade treatment-related adverse events (TRAEs), with 95% and 93% reported in the pembrolizumab combination and BRAF inhibitor only arms, respectively. Grade 3 to 5 TRAEs, however, occurred more frequently in the pembrolizumab combination arm at 58% compared with 27% in the dabrafenib plus trametinib arm. The discontinuation rate due to TRAEs was 40% and 20% in the pembrolizumab combination and dabrafenib plus trametinib arms, respectively. Common grade 3 to 5 TRAEs, which occurred in at least 5% of patients, included pyrexia, elevated ALT and/or AST, increased GGT, rash, and neutropenia. There was a death in the pembrolizumab arm caused by pneumonitis, which was deemed treatment-related. Immune-related AEs occurred in 43% of patients in the pembrolizumab group compared with 13% of patients in the BRAF inhibitor only group. The most common immune-related AEs were pneumonitis, hypothyroidism, skin disorders, hyperthyroidism, and uveitis. The authors concluded that the pembrolizumab combination “demonstrated numerically longer PFS and DoR and a higher rate of grade 3-5 TRAEs in patients with treatment-naïve BRAFV600E/K-mutant advanced melanoma.” Read more of Cancer Therapy Advisor's coverage of the ESMO 2018 meeting by visiting the conference page. Reference 1. Ascierto PA, Dummer R, et al. KEYNOTE-022 Part 3: Phase 2 randomized study of 1L dabrafenib (D) and trametinib (T) plus pembrolizumab (Pembro) or placebo (PBO) for BRAF-mutant advanced melanoma. Presented at: ESMO 2018 Congress; Munich, Germany: October 19-23, 2018. Abstract 1244O. Article Source: https://www.cancertherapyadvisor.com/esmo-2018/melanoma-pembrolizumab-dabrafenib-trametinib-shows-efficacy-adverse-effect-risk/article/809104/