乳头状肾细胞癌的最新进展.pdf

1、Updates in Papillary RCCBradley A McGregor,MDMarra Lochiatto Investigatorship in Kidney Cancer ResearchDirector of Clinical ResearchLank Center for GU Oncology,Dana Farber Cancer InstituteWhat is Papillary RCC?Papillary RCC Collecting Duct Carcinoma Tubulocystic RCC FH-Deficient RCC ALK-Translocated

2、 RCC TFE3-Transloated RCC Biphasic Hyalinizing Psammomatous RCC UnclassifiedAdapted from Michelle HirschMetastatic pRCC1 Histologically confirmed diagnosis of Papillary RCC Measurable disease 0-1 prior lines of therapy No prior therapy with sunitinib Zubrod 0-1CabozantinibCrizotinibPrimary Endpoint:

3、Progression-free survivalSecondary Endpoints:Overall survival Response rate Adverse events Exploratory evaluation of:MET mutational status MET expression SunitinibSavolitinibRandomization2Arms closed for futilityPal et al GU ASCO 2021,Lancet 2021PAPMETPAPMET-No OS benefitBarata,et al,JCO 20241.00.80

4、.60.40.20.0Probability of PFSSavolitinib(n=33)Sunitinib(n=27)03691215182124Time From Randomization(Months)332115843310271911741000SavolitinibSunitinibNumber of Patients at RiskNumber Randomized/Number of Events33/1727/20Median PFS by BICR in months(95%CI)Savolitinib 7.0(2.8,NC)Sunitinib 5.6(4.1,6.9)

5、HR(95%CI):0.71(0.37,1.36)Log-rank two-sided P-value:0.313Censored observations+Savolitinib(n=33)Sunitinib(n=27)Overall Response Rate(by BICR)9(27%)2(7%)Add Durvalumab 57%ORRChoueiri ASCO 2020,Rodriguez et al,ASCO 2021SAVOIR Genomic driven approachAWAIT SAMETAFH-Deficient RCC(N=43)Sporadic Papillary

6、RCC(N=40)ORR(95%CI)72(5783)(N=31)35(2251)(N=14)Best response no.(%)Complete response2(5)0Partial response29(67)14(35)Stable disease12(28)21(52)Unconfirmed partial response01(2)Progressive disease04(10)Median time to response(range)mo1.8(1.718.3)1.8(1.77.3)Median duration of respo