Me five|Problem 3|Zhao M et al . Advances in endocrine-resistant breast cancerTable 1 Clinical trials of targeted agents in endocrine resistant breast cancerAgent Class Style of study Study style Patient population Status/Results Ref.Targeting receptor tyrosine kinases signaling pathway PI3K/AKT/mTOR Everolimus mTOR inhibitor Phase Exemestane randomized +/everolimus Everolimus mTOR inhibitor Phase Tamoxifen +/randomized everolimus Temsirolimus mTOR inhibitor Everolimus Sirolimus mTOR inhibitor mTOR inhibitor Phase randomized Phase randomized Phase / Letrozole +/temsirolimus Letrozole +/everolimus Tamoxifen +/- sirolimusER+/HER2- LABC/MBC pts failed preceding therapy using a nonsteroidal AI ER+/HER2- MBC pts right after preceding therapy with AIPFS: ten.six vs 4.1 mo, HR 0.36; P 0.001, favoring combination arm[76]BkmPan-PI3K inhibitorPhase randomizedFulvestrant + BMKBkmPan-PI3K inhibitorPhase bFulvestrant + BMK120 Letrozole + BEZ235 Letrozole +BMK120 or BEZ235 Letrozole +XL147 or XLBez235 BMK120 or BEZ235 XL147 or XLDual PI3K-mTOR Phase b inhibitor Pan-PI3K Phase b inhibitor Pan-PI3K inhibitors/dual PI3K/mTOR inhibitor dual PI3K/ mTOR inhibitor Phase /CBR: 61 vs 42 ; TTP: eight.five vs 4.five mo, P = 0.008, favoring mixture arm First line therapy for sufferers No difference in CBR, terminated with ER positive MBC early Neoadjuvant therapy in ER + RR (by U/S): 58 vs 47 ; P = breast cancer 0.035, favoring combination arm Pts with ER+ MBC N = 400, TAM + SIR: 193; TAM alone: 207), ORR: TAM + SIR 40 ; TAM alone four ; Time to progression: TAM + SIR: 11 mo TAM alone: three mo ER+/HER2- LABC/MBC Postmenopausal pts, AI Treated, Progressed on or After mtor Inhibitor Postmenopausal pts with Ongoing, to figure out the ER+ MBC maximum tolerated dose of BKM120 Postmenopausal pts with ER+ MBC Postmenopausal pts with ER+ MBC ER+/HER2- MBC pts refractory to a prior AI therapy[77][78] [75] Bhattacharyya et al Eur.J.Cancer 47, Abstract 16LBA (2011) NCTNCTNCT01248494 NCTNCTGDC-0941 or GDC-Phase randomizedGdc-0032 BylPI3K inhibitor PI3K- inhibitorPhase / PhaseMkAKT inhibitorPhaseMkAKT inhibitorPhaseAzdAKT inhibitorPhase /Fulvestrant Portion : ER+/HER2+GDC-0941 or postmenopausal LABC/ MBC GDC-0980 refractory to AI; aspect : aspect criteria pluspik3 camutation GDC-0032 + ER+/HER2- LABC/MBC fulvestrant Postmenopausal pts BYL719 + ER+/HER2- LABC/MBC pts letrozole or exemestane Endocrine Postmenopausal pts with therapy + ER+ MBC MK2206 MK2206 LABC/LRBC/MBC monotherapy withpik3ca mutation or AKT mutation or PTEN loss Paclitaxel +/- Parta: all MBC, partb: ER+ AZD5363 MBC, stratified by PIK3CA mutation Addition of AMG 479 to either exemestane or fulvestrant BMS-754807 +/- letrozole MBC or LABC pts who had progressed on prior endocrine therapy No statistically considerable difference in PFS (PFS: three.Bis(pyridine)iodonium tetrafluoroborate uses 9 vs five.Buy8-Bromoimidazo[1,5-a]pyridine 7 mo, favoring placebo arm, P = 0.PMID:35567400 44), OS or CBT amongst two armsNCTNCT01296555 NCTNCTNCTNCTIgf-1r AmgIGF1R mABPhase randomized[87]dual IGF-1R/ insulin receptor kinase inhibitor Dalotuzumab IGF1R mAB (MK-0646)Bms-Phase randomized Phase /MBC or LA BC pts who had progressed on prior nonsteroidal AI MK-0646 and ER+/HER2- MBC pts fulvestrant without the need of prior therapy in and dasatinib metastatic settingNCTNCTWJCO|wjgnetAugust ten, 2014|Volume five|Issue 3|Zhao M et al . Advances in endocrine-resistant breast cancerCixutumumab IGF1R mAB Phase / Cixutumumab and temsirolimus Ridaforolimus and dalotuzumab vs common care MBC or LA BC pts progressed on on a single to two chemotherapy Er + bc NCTRidaforolimus (m.