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【2017ASCO-GU】Atezolizumab用于治疗膀胱癌研究：IMvigor 210结果更新

2017年02月19日

整理：大叔

来源：大叔快评

2017年ASCO GU刚刚在美国奥兰多落幕（2月16日-18日），按照惯例ASCO GU是继ASCO GI之后的第二场专科全球大会，吸引了来自世界各地泌尿系统的肿瘤专家，聚集一堂，展示和分享各自基础研究和临床研究进展。免疫检查点抑制剂（checkpoints-inhibitors）依然是热点，PD-1 /PD-L1 抑制剂在膀胱癌和肾癌的临床研究结果令人期待。

Atezolizumab（PD-L1抑制剂）是第一个获得美国食品药品监督管理局（U.S Food and Drug Administration, FDA）批准治疗2线晚期膀胱癌的检查点抑制剂，基于其注册临床研究IMvigor210的结果，FDA于2016年5月18日批准atezolizumab用于治疗局部晚期或转移性尿路上皮癌患者，在含铂类化疗方案治疗中或治疗后疾病出现进展；或在含铂类化疗方案术前新辅助或术后辅助治疗的12个月内。

Atezolizumab安全性和疗效的主要数据来自一项关键的开放标签、单臂、Ⅱ期临床研究IMvigor 210。该研究的队列2共纳入310名局部晚期或转移性尿路上皮癌患者，静脉给药1200mg/3周，直到无任何临床获益。主要临床终点为客观缓解率（ORR），次要临床终点为缓解持续时间、总体生存、无进展生存和安全性。研究还对肿瘤浸润淋巴细胞的PD-L1表达情况与治疗反应进行分析。

对于所有患者，14.8%出现一定程度肿瘤缩小，持续缓解时间从2.1个月到13.8个月不等。

所有患者都有不同程度的客观缓解，但缓解率和PD-L1在肿瘤浸润免疫细胞的表达情况有关，PD-L1阳性的患者缓解率为26%；而对于PD-L1阴性的患者，缓解率仅有9.5%。

治疗相关不良反应（AE）中，最常见主要有疲劳、食欲减退、尿路感染、发热、便秘。15%的患者出现3-4级AE，4%的患者出现3-4级免疫介导AE。未发现肾损害。

由于PD-L1表达与Atezolizumab的治疗反应相关，将该PD-L1抑制剂用于治疗局部晚期或转移性尿路上皮癌前，需要检测肿瘤浸润淋巴细胞中的PD-L1表达。因此，FDA批准了免疫组化VENTANA PD-L1检测试剂盒（SP142）作为临床补充诊断（complementary diagnosis）。

2017 ASCO GU IMvigor 210研究更新数据如下：截至于2016年7月4日的随访21个月的数据，所有患者ORR 16%，中位OS 7.9个月。

2017年2月2日FDA批准第二个治疗2线膀胱癌的PD-1抑制剂，该药用于治疗局部晚期或转移性泌尿道上皮癌适应症。完整准确的适应症措辞如下：用于治疗含铂化疗进展后或含铂化疗新辅助或辅助治疗12个月内进展的局部晚期或转移性泌尿道上皮癌（与atezolizumab适应症措辞一样），但是没要求检测PD-L1表达作为临床补充诊断。

该适应症的批准基于一项270例患者的单臂临床研究，该研究纳入治疗含铂化疗进展后或含铂化疗新辅助或辅助治疗12个月内进展的局部晚期或转移性泌尿道上皮癌患者。患者接受该药物 3mg/kg 每2周一次治疗，直至疾病进展或出现不可耐受的毒性。以RECIST (Response Evaluation Criteria in Solid Tumors )1.1为标准，独立放射评估委员会评估的客观反应率（ORR）为19.6%（53/270， 95% CI 15.1，24.9）。7例患者完全缓解，46例患者部分缓解。预计的中位反应时间为10.3个月（在数据截止时间，反应还在继续）。

最常见的不良反应（至少20%）为疲乏、肌肉关节痛、恶心和食欲减退。14例患者死于非疾病进展，其中包括4例患者死于与该药物有关的肺炎或心血管衰竭。不良反应导致17%的患者治疗剂量中断。该适应症推荐治疗剂量和周期为240mg 每2周一次，静脉注射。

Atezolizumab (atezo) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): Outcomes by prior therapy.

Abstract No:

323

Author(s): Jose Luis Perez-Gracia,

Background:

Atezo is approved in the US for mUC and non-small cell lung cancer after prior treatment with chemotherapy. > 40% of mUC pts in the Phase 2 IMvigor210 study received ≥ 2prior metastatic regimens (Rosenberg, Lancet 2016). This analysis was performed to assess the impact of prior therapy on atezo outcomes in mUC. Methods: mUC pts in the platinum-pretreated IMvigor210 cohort (NCT02108652) received atezo 1200 mg IV q3w until loss of clinical benefit. Study endpoints analyzed by the number of prior treatment regimens included RECIST v1.1 ORR (central review), complete response (CR) rate, median durations of response (mDOR) and survival (mOS) and adverse event rate.

Results:

Evaluable pts (N = 310) had a median age of 66 years, and 78% had visceral mets (31% liver). 82% of pts had prior systemic treatment for mUC; number of prior regimens ranged from 1 to ≥ 4 (Table). 73% of pts received prior cisplatin, and 26% had carboplatin (no cisplatin). Objective responses, including CRs, occurred regardless of the number of prior therapies and were ongoing in 65% of responders at the July 4, 2016 data cut off (median follow-up, 21 mo [range, 0.2+-24.5]). mDOR was not reached in any subgroup based on number of treatments, except in pts who received only perioperative chemotherapy (mDOR, 16 mo [95% CI: 6.2, NE]). Similarly, mOS was generally consistent despite number of prior regimens (Table). Atezo remained generally well tolerated with similar overall safety and tolerability by line of therapy.

Conclusions:

Clinically meaningful benefit was observed in pts treated with atezo notwithstanding number of prior systemic mUC regimens. Minimally and heavily pre-treated pts had durable responses, encouraging OS and no major differences in safety signals.

Clinical trial information:

NCT02108652

参考文献：

http://abstracts.asco.org/197/AbstView_197_179258.html

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf

编辑：肿瘤资讯-小编

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