A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC.
A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC.
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DOI：
10.1016/j.jtho.2018.03.035
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Garon EB
中科院分区：
文献类型：
--
作者：
Lisberg A;Cummings A;Goldman JW;Bornazyan K;Reese N;Wang T;Coluzzi P;Ledezma B;Mendenhall M;Hunt J;Wolf B;Jones B;Madrigal J;Horton J;Spiegel M;Carroll J;Gukasyan J;Williams T;Sauer L;Wells C;Hardy A;Linares P;Lim C;Ma L;Adame C;Garon EB
尽管派姆单抗在非小细胞肺癌 (NSCLC) 中具有显着的抗肿瘤活性，但与 EGFR 野生型患者相比，在肿瘤存在表皮生长因子受体 (EGFR) 突变的患者中观察到的临床获益较少。我们在 KEYNOTE-001 试验中的单中心经验表明，接受派姆单抗治疗的 EGFR 突变患者（未接受过酪氨酸激酶抑制剂 (TKI)）的临床结果优于之前接受 TKI 治疗的患者。由于 TKI 初治 EGFR 突变体通常被排除在派姆单抗研究之外，因此缺乏指导该患者群体治疗决策的数据，特别是 PD-L1 表达≥50% 的患者。我们在患有 EGFR 突变阳性、晚期 NSCLC 和 PD-L1 阳性（≥1%，22C3 抗体）肿瘤的 TKI 初治患者中进行了派姆单抗 II 期试验 (NCT02879994)。帕博利珠单抗每三周给药 200 毫克。主要终点是客观缓解率。次要终点包括派姆单抗的安全性、额外的派姆单抗疗效终点以及派姆单抗后 EGFR TKI 的疗效和安全性。 25 名计划患者中的 11 名接受治疗后，由于缺乏疗效而停止入组。 82% 的试验患者未接受过治疗，64% 具有 EGFR 敏感突变，73% 的 PD-L1 表达≥50%。只有 1 名患者获得客观缓解（ORR：9%），但对该患者肿瘤的重复分析明确表明 EGFR 突变的原始报告是错误的。观察到的治疗相关不良事件与之前使用派姆单抗的经历相似，但入组 6 个月内发生的两例死亡（其中 1 例归因于肺炎）值得关注。派姆单抗对未接受过 TKI 治疗、PD-L1+、EGFR 突变的晚期 NSCLC 患者（包括 PD-L1 表达≥50% 的患者）缺乏疗效，表明在这种情况下它不是合适的治疗选择。
Despite the significant antitumor activity of pembrolizumab in non-small cell lung cancer (NSCLC), clinical benefit has been less frequently observed in patients whose tumors harbor epidermal growth factor receptor (EGFR) mutations compared to EGFR wild-type patients. Our single center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI naïve EGFR-mutants have generally been excluded from pembrolizumab studies, data to guide treatment decisions in this patient population is lacking, particularly in patients with PD-L1 expression ≥50%. We conducted a phase II trial (NCT02879994) of pembrolizumab in TKI naive patients with EGFR mutation positive, advanced NSCLC and PD-L1 positive (≥1%, 22C3 antibody) tumors. Pembrolizumab was administered 200mg q3wks. The primary endpoint was objective response rate. Secondary endpoints included safety of pembrolizumab, additional pembrolizumab efficacy endpoints, and efficacy and safety of an EGFR TKI after pembrolizumab. Enrollment was ceased due to lack of efficacy after 11 of 25 planned patients were treated. 82% of trial patients were treatment naïve, 64% had sensitizing EGFR mutations, and 73% had PD-L1 expression ≥50%. Only 1 patient had an objective response (ORR: 9%), but repeat analysis of this patient’s tumor definitively showed the original report of an EGFR mutation to be erroneous. Observed treatment related adverse events were similar to prior experience with pembrolizumab, but two deaths within 6 months of enrollment, including one attributed to pneumonitis, were of concern. Pembrolizumab’s lack of efficacy in TKI naïve, PD-L1+, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression ≥50%, suggests that it is not an appropriate therapeutic choice in this setting.
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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：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
3.7
作者：
Im JS;Herrmann AC;Bernatchez C;Haymaker C;Molldrem JJ;Hong WK;Perez-Soler R
通讯作者：
Perez-Soler R
DOI：
10.1158/1078-0432.ccr-15-3101
发表时间：
2016-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Gainor JF;Shaw AT;Sequist LV;Fu X;Azzoli CG;Piotrowska Z;Huynh TG;Zhao L;Fulton L;Schultz KR;Howe E;Farago AF;Sullivan RJ;Stone JR;Digumarthy S;Moran T;Hata AN;Yagi Y;Yeap BY;Engelman JA;Mino-Kenudson M
通讯作者：
Mino-Kenudson M
影响因子：
158.5
作者：
Soria, J. -C.;Ohe, Y.;Nguyen, Nhung
通讯作者：
Nguyen, Nhung