Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial.
Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial.
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DOI：
10.1001/jamaoncol.2021.2301
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发表时间：
2021-06-04
期刊：
影响因子：
28.4
通讯作者：
Reck M
中科院分区：
文献类型：
--
作者：
Jabbour SK;Lee KH;Frost N;Breder V;Kowalski DM;Pollock T;Levchenko E;Reguart N;Martinez-Marti A;Houghton B;Paoli JB;Safina S;Park K;Komiya T;Sanford A;Boolell V;Liu H;Samkari A;Keller SM;Reck M
这项非随机试验评估了pembrolizumab联合同步放化疗治疗III期非小细胞肺癌的疗效和安全性。帕博利珠单抗联合同步放化疗（cCRT）治疗局部晚期III期非小细胞肺癌（NSCLC）患者是否安全有效？在这项非随机2队列试验中，帕博利珠单抗联合cCRT显示队列A（n = 112;鳞状/非鳞状）和队列B（n = 102;非鳞状）的客观缓解率分别为70.5%和70.6%。队列A和队列B中3级或以上肺炎的发生率分别为8.0%和6.9%。这项2队列试验的结果表明，帕博利珠单抗联合cCRT具有稳健的抗肿瘤活性，安全性可控，可能是既往未经治疗的局部晚期III期NSCLC患者的一种有前景的治疗方法。帕博利珠单抗联合同步放化疗（cCRT）给药可为局部晚期III期非小细胞肺癌（NSCLC）患者提供治疗获益。评价帕博利珠单抗联合cCRT治疗III期NSCLC的治疗结局和安全性。这项2期、非随机、2队列、开放标签的KEYNOTE-799研究在2018年11月5日至2020年7月31日期间招募了来自10个国家52个学术机构和社区机构的患者。截至2020年10月28日，队列A的中位（范围）随访时间为18.5（13.6-23.8）个月，队列B为13.7（2.9-23.5）个月。在筛选的301例患者中，入组了216例符合条件的既往未接受过治疗、不可切除且经病理学/放射学证实的IIIA/IIIB/IIIC期NSCLC患者，根据实体瘤疗效评价标准第1.1版（RECIST v1.1），这些患者具有可测量的疾病。队列A（鳞状/非鳞状）中的患者接受1个周期（3周）的卡铂（曲线下面积[AUC] 6 mg/mL/min）、紫杉醇（200 mg/m2）和帕博利珠单抗（200 mg），随后接受卡铂（AUC 2 mg/mL/min）和紫杉醇（45 mg/m2）每周一次，持续6周，以及2个周期的帕博利珠单抗加标准胸部放疗。队列B（非鳞状细胞癌）中的患者接受了3个周期的顺铂（75 mg/m2）、培美曲塞（500 mg/m2）和派姆单抗（200 mg），每3周一次，并在第2周期和第3周期接受胸部放疗。患者接受了14个额外周期的pembrolizumab治疗。共同主要终点为盲态独立中心审查的RECIST v1.1的客观缓解率和3 - 5级肺炎的发生率。队列A中共有112例患者接受治疗（76例男性[67.9%];中位[范围]年龄66.0 [46-90]岁; 66例患者[58.9%]程序性细胞死亡配体1 [PD-L1]肿瘤比例评分≥1%）和102例患者在队列B中接受治疗（62例男性[60.8%];中位[范围]年龄为64.0 [35-81]岁; 40例患者[39.2%]的PD-L1肿瘤比例评分≥1%）。队列A的客观缓解率为70.5%（79/112; 95% CI，61.2%-78.8%），队列B为70.6%（72/102; 95% CI，60.7%-79.2%）。未达到中位缓解持续时间，但分别有79.7%和75.6%的患者的缓解持续时间为12个月或更长。队列A中9/112例患者（8.0%）和队列B中7/102例患者（6.9%）发生3级或以上肺炎。112例患者中有72例（64.3%）和102例患者中有51例（50.0%）发生3 - 5级治疗相关不良事件。这项2期、非随机、2队列研究的结果表明，帕博利珠单抗联合cCRT在既往未经治疗的局部晚期III期NSCLC患者中具有良好的抗肿瘤活性和可管理的安全性。
This nonrandomized trial evaluates the treatment outcomes and safety of pembrolizumab plus concurrent chemoradiation therapy in stage III non–small cell lung cancer. Is administration of pembrolizumab plus concurrent chemoradiation therapy (cCRT) effective and safe in patients with locally advanced, stage III non–small cell lung cancer (NSCLC)? In this nonrandomized 2-cohort trial, pembrolizumab plus cCRT demonstrated objective response rates of 70.5% in cohort A (n = 112; squamous/nonsquamous) and 70.6% in cohort B (n = 102; nonsquamous). The incidence of grade 3 or higher pneumonitis was 8.0% in cohort A and 6.9% in cohort B. The findings of this 2-cohort trial suggest robust antitumor activity of pembrolizumab plus cCRT with manageable safety that may represent a promising therapy in patients with previously untreated, locally advanced, stage III NSCLC. Administration of pembrolizumab plus concurrent chemoradiation therapy (cCRT) may provide treatment benefit to patients with locally advanced, stage III non–small cell lung cancer (NSCLC). To evaluate treatment outcomes and safety of pembrolizumab plus cCRT in stage III NSCLC. The phase 2, nonrandomized, 2-cohort, open-label KEYNOTE-799 study enrolled patients between November 5, 2018, and July 31, 2020, from 52 academic facilities and community-based institutions across 10 countries. As of October 28, 2020, median (range) follow-up was 18.5 (13.6-23.8) months in cohort A and 13.7 (2.9-23.5) months in cohort B. Of 301 patients screened, 216 eligible patients with previously untreated, unresectable, and pathologically/radiologically confirmed stage IIIA/IIIB/IIIC NSCLC with measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) were enrolled. Patients in cohort A (squamous/nonsquamous) received 1 cycle (3 weeks) of carboplatin (area under the curve [AUC] 6 mg/mL/min), paclitaxel (200 mg/m2), and pembrolizumab (200 mg), followed by carboplatin (AUC 2 mg/mL/min) and paclitaxel (45 mg/m2) once weekly for 6 weeks and 2 cycles of pembrolizumab plus standard thoracic radiotherapy. Patients in cohort B (nonsquamous) received 3 cycles of cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and pembrolizumab (200 mg) every 3 weeks and thoracic radiotherapy in cycles 2 and 3. Patients received 14 additional cycles of pembrolizumab. Coprimary end points were objective response rate per RECIST v1.1 by blinded independent central review and incidence of grade 3 to 5 pneumonitis. A total of 112 patients received treatment in cohort A (76 men [67.9%]; median [range] age, 66.0 [46-90] years; 66 patients [58.9%] with programmed cell death ligand 1 [PD-L1] tumor proportion score ≥1%) and 102 patients received treatment in cohort B (62 men [60.8%]; median [range] age, 64.0 [35-81] years; 40 patients [39.2%] with PD-L1 tumor proportion score ≥1%). Objective response rate was 70.5% (79 of 112; 95% CI, 61.2%-78.8%) in cohort A and 70.6% (72 of 102; 95% CI, 60.7%-79.2%) in cohort B. Median duration of response was not reached, but 79.7% and 75.6%, respectively, had response duration of 12 months or longer. Grade 3 or higher pneumonitis occurred in 9 of 112 patients (8.0%) in cohort A and 7 of 102 (6.9%) in cohort B. Grade 3 to 5 treatment-related adverse events occurred in 72 of 112 (64.3%) and 51 of 102 (50.0%) patients, respectively. The findings of this phase 2, nonrandomized, 2-cohort study suggest promising antitumor activity of pembrolizumab plus cCRT and manageable safety in patients with previously untreated, locally advanced, stage III NSCLC.
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影响因子：
51.1
作者：
Bradley, Jeffrey D.;Paulus, Rebecca;Komaki, Ritsuko;Masters, Gregory;Blumenschein, George;Schild, Steven;Bogart, Jeffrey;Hu, Chen;Forster, Kenneth;Magliocco, Anthony;Kavadi, Vivek;Garces, Yolanda I.;Narayan, Samir;Iyengar, Puneeth;Robinson, Cliff;Wynn, Raymond B.;Koprowski, Christopher;Meng, Joanne;Beitler, Jonathan;Gaur, Rakesh;Curran, Walter, Jr.;Choy, Hak
通讯作者：
Choy, Hak
影响因子：
6.2
作者：
Durm, Greg A.;Jabbour, Salma K.;Hanna, Nasser H.
通讯作者：
Hanna, Nasser H.
影响因子：
2.6
作者：
Agulnik, J.;Kasymjanova, G.;Small, D.
通讯作者：
Small, D.
影响因子：
20.4
作者：
Peters, Solange;Felip, Enriqueta;De Ruysscher, Dirk
通讯作者：
De Ruysscher, Dirk
影响因子：
28.4
作者：
Jabbour, Salma K.;Berman, Abigail T.;Malhotra, Jyoti
通讯作者：
Malhotra, Jyoti