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1、2023免疫检查点抑制剂提高实体瘤治愈率有些影响因子较低又是国人常发的一些水刊存在的意义之一就是方便我 梳理国内一些研究进度。昨天的文章聚焦的是围术期免疫为基础的联合治 疗方案失利的消息。原本就是极速推进的免疫治疗，必然在校正。这是既 往手术、放疗、化疗、靶向治疗赛道都经历过的审慎到狂热再恢复理智的 三个阶段。免疫治疗已成为癌症治疗的核心支柱。免疫检查点抑制剂(ICIs )是肿瘤免疫疗法的一个主要类别，可以重新激活先前存在的抗肿瘤免疫。最初，IQ仅被批准用于化疗后或化疗同时进行的挽救治疗 阶段的晚期和转移性肿瘤患者，整体有效率大约为20-30%。随着十年来的重大进展，ICIs作为可切除实体瘤的
2、新辅助和/或辅助疗法的临 床试验正逐步增多。这些试验取得了可喜的结果，FDA批准ICIs作为 非小细胞肺癌、黑色素瘤、三阴性乳腺癌症和膀胱癌症的新辅助或辅 助治疗药物，该名单还在继续增加。这种治疗模式意味着癌症治疗的 范式转变，因为许多早期肿瘤患者可以通过早期引入免疫治疗来获得 治愈的可能。这篇综述文章总结了基于ICI的免疫疗法的现状，强调了 IQs作为早期肿瘤新辅助和辅助治疗的临床发展前景。Fig. 1 FDA approvals of fifst-line immunotherapy for advanced/metastatc cancer图1. FDA批准的用于晚期/转移性肿瘤患者一线
3、免疫治疗方案NeoadjuvantActivated immune cells kill tumor, Immunotherapy cel,s and shrink tumors t0 Militate 、resection and prevent recurrence.E星除14翻Surgically removal Adjuvant ImmunotherapyAntibodiesSurgically removal tumorsActivated immune cells kill more tumor cells at thetumor bed and eradicate microme
4、tastasisFig. 2 Neoadjuvant vs Adjuvant Immunotherapy in solid tumors图2.实体瘤领域新辅助vs辅助免疫治疗Fig. 3 FDA approvals of neoadjuvant and adjuvant immunotherapy for localized cancer图3. FDA批准的新辅助和辅助免疫治疗研究NCTOS27O824Advance Gastric AdenocarciIII120Radical surgery after neoadjuvant2027nomaimmunotherapy (albumin P
5、acli raxel + SeggK + PD-1 inhibitor) VS adical surgery after neoad* juvant chemotherapy (albumin Pachtaxel + Seggio)NCT04882241Gastrk CancerIII120Pembrolizumab (MK-3475) Plus Chemotherapy (XP or FP) VS Pldccbo Plus Chemotherapy (XP or FP) as Neoadjuvant/Adjuvant Treatment2025GUNCT03732677Muscle Inva
6、sive Bladder CancerIII988Durvdlumab in Combination With Gemcitabine-4-Cisplatin foe Neoodjuvanx Treatment Followed by Durvalumab Alone2026NCT04700124Muscle Invasive Bladder CancerIII784Pecioperauve Enfortumab Vedotin Plus Pembrolizumab2026(MK-3475) VS Neoadjuvant Gemcitabine and CisplatinNCT042091 1
7、4Muscle-Invasive Bladder CancerIII540Neoadjuvant and Adjuvant2024(MI8C) Who Are CisplatinNivolumab Plus NKTR-214,VSIneligibleNivolumab Alone Versus Standard of CareNCT04209114MI8C ineligible for cisplatinIII540Neoadjuvant and Adjuvant Nivolumab -4- Bempeg/ NKTR-214, VS Nivolumab Alone2024vs Standard
8、 of Care w radical cystectomyNCTO47OO124 (KEYNOTE-815)CispUtirveligible Muscle InvaIII784Perioperative Enfortumab2026sive Bladder CancerVedotin 4- Pembrohzumab 1 yr VS Neoadjuvant Gemcitabine andCisplatinGYNNCT03038100Newfy-Diagnosed Stage III orIII1301Paclitaxel cartxplatin and2023Stage IV Ovarian,
9、 Fallopian Tube,atezolizumab for 6 cycles andor Primary Peritoneal Cancerbevacizumab VS paclitaxel, carboplatin and placeboHead and NeckNCTO37OO9O5Head and Neck CancerIII276Nivolumab Alone or in Combina-2024tton With Iptlimumab as Immunotherapy VS Standard Follow-upCDS 4- tumor-infiltrating lymphocy
10、tes in tumor tissueEvent-Free Survival (EFS);Pathologkal Complete Response (pCR)Overall SurvivalEvent-Free Survival；Pathological Ccxnplctc ResponseEvent-Free Survival;Pathological Complete ResponseEvent-Free Survival;Pathological Complete ResponseEvent-Free Survival;Pathological Complete ResponseEve
11、nt-Free Survival；Pathologkal Complete ResponsePFS.OSDisease Free SurvivalTable 1 Ongoing Phase 3 neoadjuvant chemoimmunotherapy trials in solid tumorsOrgn systemClinical trifllCancer typePhaseParticipant numbersTrial designEstimated study completion (year)Primary endpoint(s)LungNCT02998528 (CheckMat
12、e 816)Early Stage NSCLCIII3soNivolumab Plus Ipilimumab or2028Event-Free Survival (EFS);Nivolumab Plus Ptannum Dou-Pathological Complete Responseblot Chemotherapy VS Platinum Doublet Chemotherapy(PCR)NCT03456063 (IMpowcr030)Resectable Slaqe II, IHA, or SelectIII453Atezolizumab or Placebo in Com-2026E
13、vent Free SurvivalIHB NSCLCbination With Platinum-Based ChemotherapyNCT04025879 (CA209-77 T)Surgically Rcmovoble Early StageHI452bOeoadjuvant Chemotherapy2024Event-Free SurvivalNSCLCPlus Nivolumab VS Neoadjuvant Chemotherapy Pius Placebo, Followed by Surgkai Resection and Adjuvant Treatment Wnh Nivo
14、lumab or PlaceboNCT03425643 (KEYNOTE-671)Resectable Stage II. Ill A. andIII786Ptatinum Doublet Chemother-2026Event Free Survival; Overall SurvivalResectable IH8 (T3-4N2) NSCLCapy Pembrolizucnab (MK- 3475) Neoadjuvant/AdjuvantTherapyNCT033001 34 (AEGEAN)Resectable Stages II and III NSCLCIII800Neoadju
15、vant/Adjuvant Dur-2024Event-Free Survival；vdlumab for the Treatment of PatientsPathological Complete ResponseNCT051S7776Resectable Locally AdvancedIII72Neoadjuvant Sintilimab and2023Pathologically ccxnplete responseNSCLC Harboring no Driver MutationsPlatinunv-based ChemotherapyrateGl tractNCTO48O767
16、3NCT04648753NCT04973306Esophageal Squamcxis Cell CarcinomaResectable Locally Advanced Thordcic Esophageal Squamcxjs Cell CarcinomaEvophageal Squamous Cell CarcinomaIIIIII342500176Pembrolizumab Plus Paclitaxel and Cisplatin VS Neoadjuvant C her nor ad io t her apy Followed by SurgeryPerioperative Tor
17、tpalimab (JSOOI) Combinwi With Neoadjuvant ChemotherapyAnti-PD-1 antibody (Tislelizumab, BeiGene) combined with neo-202820262027Event Free SurvivalEvent Free SurvivalMajor pMhologK response OSadjuvant chemoradiotherapy VS neoadjuvant clienxxadiotherapy followed by minimally invasive esophagectomyNCT
18、043O4209Colorectal CancerIMII195Neoadjuvant SintiLmab Chem- ocadiotherapy2026Pathologic complete response rateNCT02743494 (CheckMate 577)Resected stage Il-Ill evophagealIII794Neoadjuvant chemoRT fol-2025Disease Free Survivalor GE juncnon cancerlowed by complete resection.NCT03765918 (Keynote 689)Sta
19、ge Ill-IVA Resectable Locore- gionally Advanced Head and Neck Squamous Cell CarcinomaIII704Pembrolizumdb as Neoadjuvant Therapy and in Combination With Standard of Care as Adjuvant Therapy2026Major Pathological Response (mPR);Event-free SurvivalNCTO5125OS5Oral Squamous Cell CarcinomaIl-Ill80Neoadjuv
20、ant Toripalimab and Albumin Paclitaxel/Cisplatm VS Docetaxel/ Cisplatin/ 5-fluo- rouracil (TPF) on Pathological Response in Patients2025Major pathologic responseNCT045S7020High-risk Nasopharyngeal CarcinomaIII200Toripalimab with neoadjuvant cis Platinum and gemcitabine VS Standard cis Platinum and g
21、emcitabine2024PFSSkinNCT04949113Macroscopk Stage III MelanomaIII420Neoadjuvant Ipilimumab Plus Nivolumab VS Standard Adjuvant Nivolumab in Macroscopc Stage III Melanoma2027Event Free SurvivalNCT04949113 (NADINA)Stage III MelanomaIII420Neoadjuvant Ipilimumab + Nivolumab (adjuvant Nivo in residual dis
22、ease x dabfafenib/tremetinib in BRAF V600 mut) VS Standard Adjuvant Nivolumab 1 yr2027Event Free SurvivalBreastNCT03725059 (KEYNOTE-7S6)Earty-Stage Estrogen Receptor- Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast CancerIII1240PemtxolizumabVS Placebo in Combnation Wit
23、h Neoadjuvant Chenxitherapy and Adjuvant Endocrine Therapy2031Event-Free Survival;Pathological Complete ResponseNCT03036488Triple Negative Breast NeoplasmsIII1174Pembrolizumab Plus Chemo therapy VS Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy2025E
24、vent-Free Survival;Pathological Complete ResponseNCT04613674Triple Negative Breast CancerIII581Camrelizumab Plus Chemorher- apy VS Placebo Plus Chemotherapy as Neoadjuvant Therapy i2023Pathological complete response rateNCTO262O28O (NeoTRIPaPDLl)TNBCHi278Neoadjuvant Atezolizumab or placebo with Carb
25、o/abraxane, surgery followed by adjuvant chemotherapy2022Event Free SurvivalNCT03726879 (IMpassionOSO) Early Hef2 + Breast Cancer III 454NCT03595592 (APTneo)Her2 + breast cancerIII 650NCT04109066 (Checkmate 7FL)High-risk. ER+. HER2-arly Breast III Cancet1200NCT03281954TNBCIII 1520Neoadjuvant Atezoli
26、zumab or 2023 Placebo wtih Neoadjuvant ddAC Followed ByTHR adjuvant Atezo 1 yr VS placebo with Her2 HP/ TDM INeoadjuvant chemotherapy 2026VS Atezolizumab + AC-TCHP VS Atezolizumab+TCHR surgery followed by adjuvant Atezo + HPNivolumab VS Placebo in 2032 Combnaton With Neoadjuvant Chemotherapy and Adj
27、uvantEndocrine TherapyNeoadjuvant Chemotherapy 2024 With Atezolizumab or Placebo Followed by Adjuvant Alezoli- zumab or PlaceboPathologKdl Complete ResponseEvent Free SurvivalPathological Complete Response. Event Free SurvivalPathologkal Complete Response, Event Free SurvivalHNSCC headneck squamous
28、cell carcinom, NSCLC non-small-cell lung cancer, TNBC triple-negative breast cancer. OS overall survival, PFS profession free survival, VS versus表1.实体瘤领域正在进行的化疗-免疫新辅助III期临床研究Table 2 Clinical trials of first-line therapies for metastatic kidney cancerTrialsCheckMate214Keynote 426Javelin 101CheckMate
29、9ERCLEARNivolumab + lpilimumab IVPembrolizumab + AxitinibAvelumab + AxitinibNivolumab + CabozantinibPembrolizumab 4- Lenvatinibq3wX4then q4W5-10 mg po bid40 mg po qd20 mg po qdNumber of 10968618866511069(3 arms)PatientsPrimary ORR. PFS and OS int/poorOS and PFSOS and PFS in PD-L1 +PFSPFS, OS and saf
30、etyendpointsORR% (vs 42 (vs 27)593 (vs 35.7)51.4 (vs 25.5)56 (vs 27)71.0 (vs 53.3%) (Len + evero) vssunitinib CR: 9 (vs 1)CR: 5.8 (vs 1.9)CR: 4.4 (vs 2.1)CR:8(vs 5)36.1 % (sunitinib)%)CR%(vs16.1%vs93%vs4.2%sunitinib%)OS hazard 0.66(0.53-0.82)0.53 (0.38-074)0.78(0.55-108)0.60(0.40-0.89)066(049-0.88)r
31、atioPFS12.4 vs 12.315.1 vs 11.113.8 vs 8.016.6 vs 8.323.9 vs 147 vs 9 2(months) HR: 098 (0.79-1.23)HR: 0.69 (0.57-0.84)HR： 0.69 (0.56-0.83)HR: 0.51 (0.41-0.64)HR: 0.39vs suni-tinibGrade46 (vs 63)62.9 (vs 58)71.2 (vs 71.5)61 (vs 51)82.4 vs 83.1 vs 71.83 and 4toxicity%(sunitinib%)Toxicity- 22 (v5 12)1
32、0.7 (vs 13.9)7.6 (vs 13 4)37.2 (vs 14.4)induceddiscontin-uation %(sunitinib%)FDA04/16/201804/22/201905/14/201901/21/202108/11/2021approvalORR objective response rate, PFS progression-free survival, OS overall survival, CR complete response, vs versus表2.转移性肾癌一线治疗研究对于这种文章，没什么好总结的，主要就是梳理完表格就行了。参考文献Ma et al.Experimental Hematology & Oncology (2023) 12:10 https:/doi.Org/10.1186/s40164-023-00372-8