Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study.
Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study.
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DOI：
10.1016/j.lungcan.2018.08.019
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Papadimitrakopoulou V
中科院分区：
文献类型：
--
作者：
Gadgeel SM;Stevenson JP;Langer CJ;Gandhi L;Borghaei H;Patnaik A;Villaruz LC;Gubens M;Hauke R;Yang JC;Sequist LV;Bachman R;Saraf S;Raftopoulos H;Papadimitrakopoulou V
晚期非小细胞肺癌（NSCLC）的铂类化疗总体获益不大，但有可能放大免疫反应。在多队列I/II期研究KEYNOTE-021（Clinicaltrials.gov，）的队列A-C中，我们评估了铂类药物双联化疗与抗程序性死亡1单克隆抗体pembrolizumab的联合治疗。既往未经治疗的无EGFR/ALK畸变的晚期NSCLC患者随机接受帕博利珠单抗2或10 mg/kg Q3 W+卡铂血清浓度-时间曲线下面积（AUC）6 mg/mL/min+紫杉醇200 mg/m2治疗（队列A，任何组织学），卡铂AUC 6 mg/mL/min+紫杉醇200 mg/m2+贝伐珠单抗15 mg/kg（队列B，非鳞状），或卡铂AUC 5 mg/mL/min加培美曲塞500 mg/m2（队列C，非鳞状），持续4个周期，然后维持派姆单抗（队列A），派姆单抗加贝伐单抗（队列B），或派姆单抗加培美曲塞（队列C）。通过设盲独立中心审查评估缓解。总体而言，74例患者接受了随机化;队列A、B和C的中位随访时间分别为21.4、16.4和17.4个月。在任一帕博利珠单抗剂量下，任何队列均未发生剂量限制性毒性。最常见的治疗相关不良事件（AE）为脱发、疲乏和恶心。队列A、B和C中分别有40%、42%和46%的患者发生治疗相关3/4级AE;分别有24%、50%和38%的患者发生可能存在免疫病因的AE。队列A、B和C的客观缓解率分别为48%、56%和75%。帕博利珠单抗联合卡铂-紫杉醇和帕博利珠单抗联合卡铂产生了令人鼓舞的抗肿瘤活性和毒性，与基于铂的化疗或帕博利珠单抗单药治疗的已知毒性一致。
Platinum-based chemotherapy for advanced non–small-cell lung cancer (NSCLC) has modest benefit overall, but has the potential to amplify immune responses. In cohorts A-C of the multicohort phase 1/2 study KEYNOTE-021 (Clinicaltrials.gov, ), we evaluated combinations of platinum-doublet chemotherapy with the anti–programmed death 1 monocloncal antibody pembrolizumab. Patients with previously untreated, advanced NSCLC without EGFR/ALK aberrations were randomized to pembrolizumab 2 or 10 mg/kg Q3W plus carboplatin area under the serum concentration-time curve (AUC) 6 mg/mL/min plus paclitaxel 200 mg/m2 (cohort A, any histology), carboplatin AUC 6 mg/mL/min plus paclitaxel 200 mg/m2 plus bevacizumab 15 mg/kg (cohort B, non-squamous), or carboplatin AUC 5 mg/mL/min plus pemetrexed 500 mg/m2 (cohort C, non-squamous) for 4 cycles followed by maintenance pembrolizumab (cohort A), pembrolizumab plus bevacizumab (cohort B), or pembrolizumab plus pemetrexed (cohort C). Response was assessed by blinded independent central review. Overall, 74 patients were randomized; median follow-up was 21.4, 16.4, and 17.4 months in cohorts A, B, and C, respectively. No dose-limiting toxicities occurred in any cohort at either pembrolizumab dose. Most frequent treatment-related adverse events (AEs) were alopecia, fatigue, and nausea. Treatment-related grade 3/4 AEs occurred in 40%, 42%, and 46% of patients in cohorts A, B, and C, respectively; AEs with possible immune etiology occurred in 24%, 50%, and 38% of patients, respectively. Objective response rates were 48%, 56%, and 75% in cohorts A, B, and C, respectively. Pembrolizumab in combination with carboplatin-paclitaxel and with pemetrexed-carboplatin yielded encouraging antitumor activity and toxicity consistent with known toxicities of platinum-based chemotherapy or pembrolizumab monotherapy.
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DOI：
10.1093/annonc/mdq020
发表时间：
2010-09
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Reck M;von Pawel J;Zatloukal P;Ramlau R;Gorbounova V;Hirsh V;Leighl N;Mezger J;Archer V;Moore N;Manegold C;BO17704 Study Group
通讯作者：
BO17704 Study Group
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
10.9
作者：
Freshwater, Tomoko;Kondic, Anna;Stone, Julie A.
通讯作者：
Stone, Julie A.
影响因子：
45.3
作者：
Nanda, Rita;Chow, Laura Q. M.;Buisseret, Laurence
通讯作者：
Buisseret, Laurence