biostudies-literatureZhou CNational Cancer InstituteNCI NIH HHSLoxo Oncology, a wholly owned subsidiary of Eli LillyNational Institutes of HealthNIH HHS1839-1850https://www.ebi.ac.uk/biostudies/studies/S-EPMC10698285biostudies-literatureUnknown389(20)<h4>Background</h4>Selpercatinib, a highly selective potent and brain-penetrant RET inhibitor, was shown to have efficacy in patients with advanced <i>RET</i> fusion-positive non-small-cell lung cancer (NSCLC) in a nonrandomized phase 1-2 study.<h4>Methods</h4>In a randomized phase 3 trial, we evaluated the efficacy and safety of first-line selpercatinib as compared with control treatment that consisted of platinum-based chemotherapy with or without pembrolizumab at the investigator's discretion. The primary end point was progression-free survival assessed by blinded independent central review in both the intention-to-treat-pembrolizumab population (i.e., patients whose physicians had planned to treat them with pembrolizumab in the event that they were assigned to the control group) and thThe New England journal of medicineFirst-Line Selpercatinib or Chemotherapy and Pembrolizumab in &lt;i&gt;RET&lt;/i&gt; Fusion-Positive NSCLC.PMC10698285R25 CA233208N/AP30 CA008748P30CA008748R01 CA2515911R01CA273224-01R01 CA2732241R01CA251591001A1Mavroudis DHuang WTRodriguez Abreu DGoeminne JCVynnychenko ONovello SGarrido-Lopez PElamin YYToschi LSantini FCOpalka PRieke DTKontakiotis TFernandez de Sanmamed MSoldatenkova VYang JCLIBRETTO-431 Trial InvestigatorsArriola Aperribay EMartinez Aguillo MSolomon BReis TChu QDeschepper KMoiseenko FKenmotsu HWei YFMorabito AHo CLBernabe Rde la Mora Jimenez ELi YCPayakachat NMelichar BKumagai TYanagitani NCicin ITiut CDemir ACappuzzo FOhashi KSakakibara JHarputluoglu HLee KYKowalyszyn RCheng YLoong HHOhe YTang KKim DWGumus MBerzoy OLee DHZhou CNechushtan HKaplan MAPinto GDNadal EWong MZhou JYu YCoves Sarto JFerreira CFan YArdizzoni ALee SHPonomarova ORozhkova IHan BReinmuth NLing CPKazantseva MArslan CLima LHan HPuri TLambrechts MWang CCHashemi SMassuti BPerol MMakarycheva YKadzhoian ADong XDooms CCiuleanu TVicente DBar JGoto KHoffknecht Pde Castro Junior GLin ABWang ZChang GCRajakumar DLeighl NLai CLPark KSinielnikov IYang NLerzo GYang MArriola ECortinovis DDudnik JTakeuchi SMartinez Bueno ASoares AKim JSAlamgeer MSchumann CMoran Bueno MTMatsishevska IOzyilkan ODrilon ABondarenko IBria EHan JYSurmont VWislez MSakamoto TAlexandru AInsa Molla ABaka SMajem MMak MPSiena SReck MLin CCZer AMigliorino MRMak MLin SHMallesara GPaz-Ares Rodriguez LBischoff HGanju VKobziev OQuantin XBiesma BKim YJViguro MWolf JBoyer MRoubec JLoong HYang CTLiutti VPaz GDingemans AMCSyrigos KPeled NDziadziuszko RYang TYGoksel TSolovyeva EMartin CKato TDemedts IZhang WLin BKOksuzoglu BLevchenko ED'Arcangelo MDe Carlo EHayashi HUh MKZhang YAlatorre Alexander JOrtega Granados ALMazilu LAguado de la Rosa CChen YMIvashchuk OMoro-Sibilot DPadoan MfalseFirst-Line Selpercatinib or Chemotherapy and Pembrolizumab in &lt;i&gt;RET&lt;/i&gt; Fusion-Positive NSCLC.<h4>Background</h4>Selpercatinib, a highly selective potent and brain-penetrant RET inhibitor, was shown to have efficacy in patients with advanced <i>RET</i> fusion-positive non-small-cell lung cancer (NSCLC) in a nonrandomized phase 1-2 study.<h4>Methods</h4>In a randomized phase 3 trial, we evaluated the efficacy and safety of first-line selpercatinib as compared with control treatment that consisted of platinum-based chemotherapy with or without pembrolizumab at the investigator's discretion. The primary end point was progression-free survival assessed by blinded independent central review in both the intention-to-treat-pembrolizumab population (i.e., patients whose physicians had planned to treat them with pembrolizumab in the event that they were assigned to the control group) and th2023-01-01T00:00:00Z2023 Nov2026-05-29T14:14:45.648Z2026-04-08T05:00:42.991ZS-EPMC106982853787097310.1056/NEJMoa230945710.1056/nejmoa2309457