PD-1/PD-L1抑制剂用于膀胱癌新辅助治疗疗效和安全性的单组率Meta分析

易小琦; 邓红彬; 李龙浩; 张渝聆; 李文聪

doi:10.6039/j.issn.1001-0408.2023.18.15

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PD-1/PD-L1抑制剂用于膀胱癌新辅助治疗疗效和安全性的单组率Meta分析

循证药学 | 更新时间：2023-09-22

- PD-1/PD-L1抑制剂用于膀胱癌新辅助治疗疗效和安全性的单组率Meta分析
- Efficacy and safety of PD-1/PD-L1 inhibitors for neoadjuvant treatment of bladder cancer： meta-analysis of single-group rates
- 中国药房 2023年34卷第18期页码：2256-2262
- 作者机构：
  
  重庆医科大学附属第一医院肿瘤科，重庆　400016
- 作者简介：
  
  硕士研究生。研究方向：各种实体瘤放射治疗与内科综合治疗。E-mail：yixq@stu.cqmu.edu.cn
  副主任医师，硕士生导师，硕士。研究方向：各种实体瘤放射治疗与内科综合治疗。E-mail：denghb@hospital.cqmu.edu.cn
- 基金信息：
  
  重庆市科卫联合医学科研项目(2021MSXM318)
- DOI：10.6039/j.issn.1001-0408.2023.18.15
  中图分类号： R979.1+9
- 纸质出版日期：2023-09-30，
  
  收稿日期：2023-02-08，
  
  修回日期：2023-08-06，
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易小琦,邓红彬,李龙浩等.PD-1/PD-L1抑制剂用于膀胱癌新辅助治疗疗效和安全性的单组率Meta分析 ^Δ[J].中国药房,2023,34(18):2256-2262.

YI Xiaoqi,DENG Hongbin,LI Longhao,et al.Efficacy and safety of PD-1/PD-L1 inhibitors for neoadjuvant treatment of bladder cancer： meta-analysis of single-group rates[J].ZHONGGUO YAOFANG,2023,34(18):2256-2262.
易小琦,邓红彬,李龙浩等.PD-1/PD-L1抑制剂用于膀胱癌新辅助治疗疗效和安全性的单组率Meta分析 ^Δ[J].中国药房,2023,34(18):2256-2262. DOI： 10.6039/j.issn.1001-0408.2023.18.15.

YI Xiaoqi,DENG Hongbin,LI Longhao,et al.Efficacy and safety of PD-1/PD-L1 inhibitors for neoadjuvant treatment of bladder cancer： meta-analysis of single-group rates[J].ZHONGGUO YAOFANG,2023,34(18):2256-2262. DOI： 10.6039/j.issn.1001-0408.2023.18.15.

摘要

目的

评价程序性死亡受体1（PD-1）/程序性死亡配体1（PD-L1）抑制剂用于膀胱癌新辅助治疗的疗效和安全性，为临床治疗提供循证依据。

方法

计算机检索PubMed、the Cochrane Library、Embase、American Society of Clinical Oncology Meeting Library、中国知网、维普网及万方数据等，收集PD-1/PD-L1抑制剂用于膀胱癌新辅助治疗的随机对照试验（RCT）、非RCT、病例对照研究、队列研究等，检索时限为建库起至2023年1月31日。筛选文献，提取资料及质量评价后，采用RevMan 5.3软件进行单组率Meta分析，采用Stata12软件进行敏感性分析和发表偏倚分析。

结果

共纳入25项研究，共计940例患者。Meta分析结果显示，患者的病理完全缓解（pCR）率为32%[OR＝0.32，95%CI（0.22，0.45），

＝0.006]，降期率为52%[OR＝0.52，95%CI（0.45，0.60），

＝0.55]，3级及以上免疫相关不良反应（Grade≥3 irAEs）发生率为16%[OR＝0.16，95%CI（0.11，0.22），

＜0.000 01]。亚组分析结果显示，pCR率和Grade≥3 irAEs 发生率在单用PD-1/PD-L1抑制剂患者中分别为25%、9%，在联合免疫治疗患者中分别为29%、28%，在PD-1/PD-L1抑制剂联合化疗患者中分别为43%、12%；PD-L1阳性患者的pCR率为44%，PD-L1阴性患者为25%。敏感性分析结果显示，本研究所得结果稳健。发表偏倚分析结果显示，本研究存在发表偏倚可能性较小。

结论

PD-1/PD-L1抑制剂用于膀胱癌新辅助治疗的疗效和安全性均较好。

Abstract

OBJECTIVE

To evaluate the efficacy and safety of PD-1/PD-L1 inhibitors for neoadjuvant treatment of bladder cancer， and to provide evidence-based reference for clinical treatment.

METHODS

Retrieved from PubMed， Cochrane Library， Embase， American Society of Clinical Oncology Meeting Library， CNKI， VIP and Wanfang database， etc.， the randomized controlled trials （RCTs）， non-RCT， case-control studies， cohort studies， etc. about PD-1/PD-L1 inhibitors for neoadjuvant treatment of bladder cancer were collected from the inception to Jan 31st， 2023. After literature screening， data extraction and quality evaluation， RevMan 5.3 software was used to perform meta-analysis of single-group rates； sensitivity analysis and publication bias analysis were conducted using Stata12 software.

RESULTS

A total of 25 studies were included in this discussion， involving 940 patients. The results of meta-analysis showed that the pathologic complete response （pCR） rate was 32% [OR＝0.32，95%CI （0.22， 0.45），

＝0.006]， downstaging rate was 52% [OR＝0.52， 95%CI （0.45， 0.60），

＝0.55]， and the incidence of ≥grade 3 immune-related adverse events （irAEs） was 16% [OR＝0.16， 95%CI （0.11， 0.22），

＜0.000 01]. Subgroup analysis showed that the patients receiving PD-1/PD-L1 inhibitors alone had a pCR rate of 25% and a incidence of Grade≥3 irAEs of 9%； the patients receiving combined immunotherapy had a pCR rate of 29% and a incidence of Grade≥3 irAEs of 28%； the patients receiving PD-1/PD-L1 inhibitors combined with chemotherapy had a pCR rate of 43% and a incidence of Grade≥3 irAEs of 12%； PD-L1 positive patients had a pCR rate of 44%， and PD-L1 negative patients had a pCR rate of 25%. The results of the sensitivity analysis showed that the study was robust. The results of the publication bias analysis showed that there was no significant publication bias.

CONCLUSIONS

PD-1/PD-L1 inhibitors are effective and safe for adjuvant treatment of bladder cancer.

关键词

膀胱癌程序性死亡受体1程序性死亡配体1新辅助治疗单组率Meta分析疗效安全性

Keywords

programmed death receptor-1programmed death-ligand 1neoadjuvant treatmentmeta-analysis of single-group ratesefficacysafety

references

BILIM V，KUROKI H，SHIRONO Y，et al. Advanced bladder cancer：changing the treatment landscape[J]. J Pers Med，2022，12（10）：1745.

YIN P N，KC K，WEI S S，et al. Histopathological distin-ction of non-invasive and invasive bladder cancers using machine learning approaches[J]. BMC Med Inform Decis Mak，2020，20（1）：162.

PATIL G，BASU A. Emerging perioperative therapeutic approaches in muscle invasive bladder cancer[J]. Ther Adv Urol，2022，14：17562872221134389.

FLAIG T W，SPIESS P E，ABERN M，et al. NCCN guidelines® insights：bladder cancer，version 2.2022[J]. J Natl Compr Canc Netw，2022，20（8）：866-878.

Advanced Bladder Cancer（ABC）Meta-analysis Collaborators Group. Adjuvant chemotherapy for muscle-invasive bladder cancer：a systematic review and meta-analysis of individual participant data from randomised controlled trials [J]. Eur Urol，2022，81（1）：50-61.

WITJES J A，BRUINS H M，CATHOMAS R，et al. European association of urology guidelines on muscle-invasive and metastatic bladder cancer：summary of the 2020 guidelines[J]. Eur Urol，2021，79（1）：82-104.

陈月红，杜亮，耿兴远，等. 无对照二分类数据的Meta分析在RevMan软件中的实现[J]. 中国循证医学杂志，2014，14（7）：889-896.

PEYROTTES A，OUZAID I，CALIFANO G，et al. Neoadjuvant immunotherapy for muscle-invasive bladder cancer[J]. Medicina（Kaunas），2021，57（8）：769.

SLIM K，NINI E，FORESTIER D，et al. Methodological index for non-randomized studies（minors）：development and validation of a new instrument[J]. ANZ J Surg，2003，73（9）：712-716.

BAÑARES R，ALBILLOS A，RINCÓN D，et al. Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding：a meta-analysis[J]. Hepatology，2002，35（3）：609-615.

刘曼，陈文松，刘玉秀，等. 单组率研究含零事件的Meta分析方法[J]. 中国循证医学杂志，2020，20（10）：1226-1233.

MARTINEZ CHANZA N，SOUKANE L，BARTHELEMY P，et al. Avelumab as neoadjuvant therapy in patients with urothelial non-metastatic muscle invasive bladder cancer：a multicenter，randomized，non-comparative，phase Ⅱ study（Oncodistinct 004 - AURA trial）[J]. BMC Cancer，2021，21（1）：1292.

RODRIGUEZ-MORENO J F，DE VELASCO G，ALVAREZ-FERNANDEZ C，et al. 761P Impact of the combination of durvalumab（MEDI4736） plus olaparib（AZD2281） admini-stered prior to surgery in the molecular profile of resectable urothelial bladder cancer. NEODURVARIB trial[J]. Ann Oncol，2020，31：S589.

GAO J J，NAVAI N，ALHALABI O，et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma[J]. Nat Med，2020，26（12）：1845-1851.

VAN DIJK N，GIL-JIMENEZ A，SILINA K，et al. Pre-operative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer：the NABUCCO trial[J]. Nat Med，2020，26（12）：1839-1844.

NECCHI A，RAGGI D，GALLINA A，et al. Updated results of PURE-01 with preliminary activity of neoadjuvant pembrolizumab in patients with muscle-invasive bladder carcinoma with variant histologies[J]. Eur Urol，2020，77（4）：439-446.

POWLES T，KOCKX M，RODRIGUEZ-VIDA A，et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial[J]. Nat Med，2019，25（11）：1706-1714.

GUPTA S，GIBB E，SONPAVDE G P，et al. Biomarker analysis and updated clinical follow-up from BLASST-1（bladder cancer signal seeking trial）of nivolumab，gemcitabine，and cisplatin in patients with muscle-invasive bladder cancer（MIBC）undergoing cystectomy[J]. J Clin Oncol，2022，40（6_suppl）：528.

CATHOMAS R，PETRAUSCH U，HAYOZ S，et al. Perioperative chemoimmunotherapy with durvalumab（Durva）in combination with cisplatin/gemcitabine（Cis/Gem）for operable muscle-invasive urothelial carcinoma（MIUC）：preplanned interim analysis of a single-arm phase Ⅱ trial（SAKK 06/17）[J]. J Clin Oncol，2020，38（6_suppl）：499.

GALSKY M D，DANESHMAND S，CHAN K G，et al. Phase 2 trial of gemcitabine，cisplatin，plus nivolumab with selective bladder sparing in patients with muscle- invasive bladder cancer（MIBC）：HCRN GU 16-257[J]. J Clin Oncol，2021，39（15_suppl）：4503.

ROSE T L，HARRISON M R，DEAL A M，et al. Phase Ⅱ study of gemcitabine and split-dose cisplatin plus pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive bladder cancer[J]. J Clin Oncol，2021，39（28）：3140-3148.

FUNT S A，LATTANZI M，WHITING K，et al. Neoadjuvant atezolizumab with gemcitabine and cisplatin in patients with muscle-invasive bladder cancer：a multicenter，single-arm，phase Ⅱ trial[J]. J Clin Oncol，2022，40（12）：1312-1322.

ZHANG R Y，ZANG J Y，XIE F，et al. Longitudinal personalized urinary tumor DNA analysis in muscle-invasive bladder cancer from the neoadjuvant immunotherapy trial RJBLC-I2N003[J]. J Clin Oncol，2022，40（6_suppl）：552.

NATESAN D V，ZHANG L，OH D Y，et al. Updated results of phase Ⅱ trial using escalating doses of neoadjuvant atezolizumab for cisplatin-ineligible patients with nonmetastatic urothelial cancer（NCT02451423）[J]. J Clin Oncol，2021，39（15_suppl）：e16510.

WEI X X，ALEXANDER MCGREGOR B，LEE R J，et al. Durvalumab as neoadjuvant therapy for muscle-invasive bladder cancer：preliminary results from the Bladder Cancer Signal Seeking Trial（BLASST）-2[J]. J Clin Oncol，2020，38（6_suppl）：507.

GOUBET A G，ALVES COSTA SILVA C，LORDELLO DE MELO L，et al. Bacteria-specific CXCL13-producing follicular helper T cells are putative prognostic markers to neoadjuvant PD-1 blockade in muscle-invasive urothelial carcinoma[J]. J Clin Oncol，2022，40（6_suppl）：535.

GUERCIO B J，PIETZAK E J，BROWN S，et al. Neoadjuvant nivolumab（N）+/- ipilimumab（I）in cisplatin-ineligible patients（pts）with muscle-invasive bladder cancer（MIBC）[J]. J Clin Oncol，2022，40（6_suppl）：498.

GRIVAS P，YIN J，KOSHKIN V S，et al. PrE0807：A phase Ⅰb feasibility trial of neoadjuvant nivolumab（N）without or with lirilumab（L） in cisplatin-ineligible patients（pts）with muscle-invasive bladder cancer（MIBC）[J]. J Clin Oncol，2021，39（15_suppl）：4518.

KIM H，KIM R，HONG J，et al. A prospective phase Ⅱ trial of neoadjuvant nivolumab plus gemcitabine/cisplatin chemotherapy in muscle-invasive urothelial carcinoma of bladder[J]. J Clin Oncol，2022，40（6_suppl）：494.

XING N，HAN S，JIANG J，et al. 703P Camrelizumab in combination with gemcitabine plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer[J]. Ann Oncol，2021，32：S714.

GRANDE E，GUERRERO F，PUENTE J，et al. Dutreneo trial：a randomized phase Ⅱ trial of durvalumab and tremelimumab versus chemotherapy as a neoadjuvant approach to muscle-invasive urothelial bladder cancer（MIBC） patients（pts） prospectively selected by an interferon（INF）-gamma immune signature[J]. J Clin Oncol，2020，38（15_suppl）：5012.

THIBAULT C，ELAIDI R，VANO Y A，et al. Open-label phase Ⅱ to evaluate the efficacy of neoadjuvant dose-dense MVAC in combination with durvalumab and tremelimumab in muscle-invasive urothelial carcinoma：NEMIO[J]. Bull Cancer，2020，107（5S）：eS8-eS15.

LIN T X，LI K W，FAN J H，et al. Interim results from a multicenter clinical study of tislelizumab combined with gemcitabine and cisplatin as neoadjuvant therapy for patients with cT2-T4aN0M0 MIBC[J]. J Clin Oncol，2022，40（16_suppl）：4580.

VAN DORP J，SUELMANN B B M，MEHRA N，et al. LBA31 High- vs low-dose pre-operative ipilimumab and nivolumab in locoregionally advanced urothelial cancer（NABUCCO cohort 2）[J]. Ann Oncol，2021，32：S1305-S1306.

NECCHI A，MARTINI A，RAGGI D，et al. A feasibility study of preoperative pembrolizumab before radical nephroureterectomy in patients with high-risk，upper tract urothelial carcinoma：pure-02[J]. Urol Oncol，2022，40（1）：10.e1-10.e6.

KAIMAKLIOTIS H Z，ADRA N，KELLY W K，et al. Phase Ⅱ neoadjuvant（N-） gemcitabine（G） and pembrolizumab（P） for locally advanced urothelial cancer（LAUC）：interim results from the cisplatin（C）-ineligible cohort of GU14-188[J]. J Clin Oncol，2020，38（15_suppl）：5019.

LOWE M C，KUDCHADKAR R R. Neoadjuvant therapy for melanoma[J]. Surg Oncol Clin N Am，2020，29（3）：445-53.

YIN Z，YU M，MA T T，et al. Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer：a key role of exosomal PD-L1[J]. J Immunother Cancer，2021，9（1）：e001698.

YI M，ZHENG X，NIU M，et al. Combination strategies with PD-1/PD-L1 blockade：current advances and future directions [J]. Mol Cancer，2022，21（1）：28.

BOUTROS C，TARHINI A，ROUTIER E，et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination[J]. Nat Rev Clin Oncol，2016，13（8）：473-486.

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