b'Overall Survival Improves With Adjuvant Pembrolizumab in RCCBOSTONAthirdpre- A significant improvement inanalyses(hazardratiofor specifiedinterimanalysisoverall survival was observedrecurrenceordeath,0.72; of the KEYNOTE-564 trialwith pembrolizumab as95%confidenceinterval hasdeterminedthatadju- compared with placebo[CI], 0.59 to 0.87). vantpembrolizumabafterAsignificantimprove-surgerywasassociatedment in overall survival was with a significant and clinically meaningful im- observed with pembrolizumab as compared with provement in overall survival, as compared withplacebo (hazard ratio for death, 0.62; 95% CI, 0.44 placebo, among participants with clear-cell renal- to 0.87; P=0.005), according to the researchers. cellcarcinomaatincreasedriskforrecurrenceThe estimated overall survival at 48 months was after surgery. 91.2% in the pembrolizumab group, as compared Pembrolizumab,marketedasKeytruda,waswith 86.0% in the placebo group; the benefit was approved on the basis of a significant improvementconsistent across key subgroups.in disease-free survival in the KEYNOTE-564 trial.The study also noted that pembrolizumab was DanaFarberCancerInstitute,HarvardMedicalassociatedwithahigherincidenceofserious School and Beth Israel Deaconess Medical Center,adverseeventsofanycause(20.7%,vs.11.5% allinBostonandcolleaguesrecentlyexploredwith placebo) and of grade 3 or 4 adverse events whether the results regarding overall survival fromrelated to pembrolizumab or placebo (18.6% vs. the third prespecified interim analysis of the trial1.2%).Nodeathswereattributedtopembroli-would also favor pembrolizumab. zumab therapy, however.For the phase 3, double-blind, placebo-controlledThe authors concluded that adjuvant pembroli-trial, with results published recently in the Newzumab was associated with a significant and clini-England Journal of Medicine, the study team ran- cally meaningful improvement in overall survival, domlyassigned496participantswithclear-cellascomparedwithplacebo,amongparticipants renal-cell carcinoma who had an increased risk ofwith clear-cell renal-cell carcinoma at increased recurrence after surgery to receive 200 mg of pem- risk for recurrence after surgery.brolizumab or placebo (498 participants) every 3Theyadded,Althoughimproveddisease-free weeks for up to 17 cycles (about a years worthsurvival has been reported before with adjuvant or until recurrence, the occurrence of unacceptableanti-PD-1oranti-PD-L1therapy(e.g.,among toxic effects, or withdrawal of consent. 1 patientswithmelanoma,ourtrialalsoprovides Asignificantimprovementindisease-freeevidence of an overall survival benefit with such survivalaccordingtoinvestigatorassessmenttherapy. Cross-tumor comparisons are very com-(the primary end point) was shown previously,plex owing to the distinct immune responsiveness theauthorswrote.Overallsurvivalwastheand tumor microenvironment of different cancers.key secondary end point. Safety was a second- 1Choueiri TK, Tomczak P, Park SH, Venugopal B, et. Al.; KEY-ary end point. NOTE-564 Investigators. Overall Survival with Adjuvant Pem-As of Sept. 15, 2023, a median follow-up of 57.2brolizumab in Renal-Cell Carcinoma. N Engl J Med. 2024 Apr months, results indicated that the disease-free sur- 18;390(15):1359-1371. doi: 10.1056/NEJMoa2312695. PMID: vival benefit was consistent with that in previous38631003.64'