一线系统治疗策略.pdf

1、FIRST LINE SYSTEMIC THERAPY STRATEGIESDavid McDermott,MDBeth Israel Deaconess Medical CenterHarvard Medical SchoolDisclosure InformationEXCLUSION ZONEContent Consultant for:BMS,Pfizer,Merck,Iovance,Eisai Inc.,Werewolf Therapeutics,Synthekine,Inc.,AveoGrant/Research support from:BMS,Merck,Genetech,Pf

2、izer,Exelixis,Alkermes,Inc.Speakers Bureau for:NoneStockholder in:NoneHonoraria from:BMS,Pfizer,Merck,Iovance,Eisai Inc.,Werewolf Therapeutics,Synthekine,Inc.,AveoEmployee of:Beth Israel Deaconess Medical Center Final Results of First-line IO Combination Trials in mRCC(ITT population)1.Choueiri et a

3、l.ASCO 2025 2.Rini et al.Nature Medicne(submitted)3.Motzer et al ASCO GU 20254.Motzer et al.JCO 2024CheckMate 214(Ipi/Nivo)1(n=550 vs n=546)KEYNOTE-426(Axi/Pembro)2(n=432 vs n=429)CheckMate 9ER(Cabo/Nivo)3(n=323 vs n=328)CLEAR(Len/Pembro)4(N=355 vs n=357)OS HRmOS,months0.7152.7 vs 37.80.8447.2 vs 40

4、.80.7946.5 vs 35.50.7953.7 v.54.3Landmark OS42%at 6 years31%at 9 years42%at 5 years41%at 5 years66%at 3 yearsPFS HRmPFS,months0.8812.4 vs 12.30.6915.7 vs 11.10.5816.4 vs 8.30.4723.9 vs 9.2Landmark PFS26%at 6 years23%at 8 years18%at 5 years14%at 5 years37%at 3 yearsORR,%40 vs 3361 vs 4056 vs 2771 vs

5、37CR,%12 vs 312 vs 414 vs 518 vs 4Median f/u9.3 years5.6 years5.6 years4.2 yearsPrimary PD18%12%7%5%brian_rini and Uromigos(podcasts:https:/ the Anti-Kidney Cancer Immune Response1 Immune desertImmune excludedInflamed1Killing of cancer cells2Cancer antigenpresentation3Immune cell priming and activat

6、ion4Immune cell trafficking to tumors5Immune cell infiltration into tumors6Recognition of cancer cells by T/NK cells7Reversing T cell exhaustion4CytokinesCTLA-4 blockadeVEGF blockade2-4PD-L1,PD-1 inhibitors3.Manning EA et al.Clin Cancer Res.2007;13:3951-3959.4.Motz GT et al.Nat Med.2014;20:607-615.1