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Comprehensive Review of Navelbine.Comprehensive Review of Navelb1NavelbineOral navelbine vs.IV NavelbineEfficacyQuality of lifeConvenienceAdjuvant chemotherapy with NavelbineLace meta-analysisNavelbine in first line HistologyNavelbine in maintenance therapyNavelbine in elderlyMonotherapy.NavelbineOral navelbine vs.IV2NAVELBINE ORALNAVELBINE ORALI.V.versus ORAL2525 mg/m I.V.mg/m I.V.versus6060 mg/m ORAL mg/m ORAL3030 mg/m I.V.mg/m I.V.versus8080 mg/m ORAL mg/m ORALEquivalent AUCs:I.V.ORAL30 mg/m80 mg/m25 mg/m60 mg/mMarty,Ann.Oncol.2001NAVELBINE ORAL:for an improved convenience of treatmentNAVELBINE ORAL:for an improved convenience of treatment1101001000100000122436Time(h)Blood Conc(ng/ml)1101001000100000122436Time(h)Blood Conc(ng/ml).NAVELBINE ORALI.V.versus ORAL3NVB Oral:60 mg/m/w x3 then 80 mg/m/w versus versusNVB I.V.:30 mg/m/wStage IIIB-IVPS 0-1No history of malabsorptionJassem,Ann Oncol 2001Jassem,Ann Oncol 2001NAVELBINE I.V.versus ORAL RANDOMISED PHASE II STUDYRANDOMISED PHASE II STUDY.NVB Oral:60 mg/m/w x3 then 84NAVELBINE I.V.versus ORALRegimen Regimen mg/m weeklymg/m weeklyI.V.30 I.V.30 Oral 60/80Oral 60/80n n30307676OR OR(%)(%)11111212Disease control Disease control 48485252PFS PFS(months)(months)2.12.13.23.2MS MS(months)(months)7.97.99.39.3Neutropenia Neutropenia G3/4(%)G3/4(%)62624646Jassem,Ann Oncol 2001Jassem,Ann Oncol 2001Single agent.NAVELBINE I.V.versus ORALReg5Gridelli et al JNCI 1999,p=0.046.24.7024681012CHEMOTHERAPY REGIMENMEDIAN SURVIVAL IN MONTHS:VinorelbineSupportive Care.NON-SMALL CELL LUNG CANCER-S6Kelly J Clin Oncol 2001;Survival:1 YR 36%/38%,2 YR 15%/16%;Resp Rate:28%/25%88024681012CHEMOTHERAPY REGIMENMEDIAN SURVIVAL IN MONTHS:Vinorelbine+DDPPaclitaxel+Carbo.NON-SMALL CELL LUNG CANCER-S7Kelly J Clin Oncol 2001.(N=410).Baseline Compared with Week 25(Using FACT-L)0102030405060708090100Vinorelbine+CisplatinPaclitaxel+CarboplatinPERCENT OF PATIENTS:QL:ImpovedQL:Stable.NON-SMALL CELL LUNG CANCER-S8Evaluation of the impact on nursing and pharmacy staff resource and patient waiting time of a switch from IV to oral chemotherapy:a time and motion auditDr Henry TaylorKent Oncology Centre9Cancer Services Collaborative,31st October 2005.Evaluation of the impact on nu9Capacity PlanningFor each patient given IV chemotherapy:4 patients could have been given oral chemotherapy by nursing staff 3 patients could have had their oral chemotherapy prepared by pharmacyUnit:minute.Capacity PlanningFor each pati10Adjuvant Chemotherapy in NSCLC:A new standard of care?.Adjuvant Chemotherapy in NSCL11New Engl J Med 2004;350:351-60New Engl J Med 2004;350:351-604%.New Engl J Med 2004;350:351-6012ASCO 2005 ANITA:OS monthsSurvival Distribution Function1.000.750.500.2500204060801001200.79 0.66-0.950.79 0.66-0.95Hazard RatioHazard Ratio0.0130.013P-valueP-value65.865.843.843.8Median monthsMedian monthsNVB+CDDPNVB+CDDPOBS.OBS.ObsNVB+CDDP.ASCO 2005 ANITA:OS months13Adjuvant ChemotherapyStandard of Care Good performance status patients with“R0”Anatomic Resection -Stages IIA-B -Stages IIA-B -IIIA NSCLC -IIIA NSCLC -Maybe Larger IBMaybe Larger IB?.Adjuvant ChemotherapyStandar14JCO 2008:JCO 2008:LACELACE meta-analysis meta-analysis JTO 2010:JTO 2010:LACE NAVELBINELACE NAVELBINE meta-analysis meta-analysisLACE*LACE*meta-analysismeta-analysisLACE*NAVELBINE LACE*NAVELBINE meta-analysis meta-analysisPopulationPatients with completely resected NSCLCInclusion criteriaCDDP-based vs ObsCDDP-based+PORT*vs PORTNVB+CDDP vs ObsNVB+CDDP+PORT vs PORTIncluded studies5 studies includedALPI,BLT,IALT,JBR10,ANITA4 studies includedBLT,IALT,JBR10,ANITAPts characteristicsn=4,584IA:8%,IB:30%,II:35%,III:27%n=1,888IA:2%,IB:34%,II:38%,III:26%Main objectiveOverall Survival of CDDP-based regimensOverall Survival of NVB+CDDP regimens*LACE=Lung Adjuvant Cisplatin Evaluation*PORT=post-operative RTPignon,JCO 2008,Douillard,JTO 2010Activity of a CDDP-based doublet in an adjuvant treatmentSpecific input of NAVELBINE in a CDDP-based adjuvant treatment.JCO 2008:LACE meta-analysis 15NAVELBINE+cisplatin is the new standard of care as adjuvant treatment for NSCLCResectable NSCLC:Contribution of NVB I.V.+CDDP Resectable NSCLC:Contribution of NVB I.V.+CDDP Should adjuvant CT be NVB+CDDP?Should adjuvant CT be NVB+CDDP?6Survival(%)+5.3%withCDDP-based+8.9%with NVB+CDDPLACE NavelbinePignon,JCO 2008,Douillard,JTO 2010.NAVELBINE+cisplatin is the n16Navelbine as first line in NSCLC.Navelbine as first line in NSC17.18MEDIAN SURVIVAL(months)MEDIAN SURVIVAL(months)NAVELBINE I.V./ORAL-Cisplatin Experience(n=118(n=118)(n=206)(n=206)(n=206)(n=206)(n=202)(n=202)(n=201)(n=201)(n=140)(n=140)(n=250)(n=250)(n=204)(n=204)(n=404)(n=404)(n=137(n=137)(n=190(n=190)Phase III trials-n 2000 patientsPhase III trials-n 2000 patientsLe Chevalier Le Chevalier Wozniak Wozniak Kelly Kelly Scagliotti Scagliotti Fossella Fossella Gebbia Gebbia Gebbia Gebbia Georgoulias Georgoulias Martoni Martoni Douillard Douillard Ohe Ohe TanTan 19941994 1998 1998 2001 2001 2002 2002 2003 2003 2003 2003 2005 2005 2005 2005 20052005 2005 2005 2007 2007 20072007(n=145(n=145)NVB I.V./ORAL.MEDIAN SURVIVAL(months)NAVELB191 1stst line metastatic NSCLC line metastatic NSCLC NVB IV/Oral+Carbo experienceNVB IV/Oral+Carbo experiencen=912n=912(n=61)(n=75)(n=77)(n=83)(n=52)(n=150)(n=158)(n=156)MS(m)NVB IV/Oral(n=44)(n=56)Parente Santomaggio Bretti Cremonesi Maguire Tan Helbekkmo Jensen*OBrien*Reck*1997 1998 2001 2003 2003 2005 2007 2007 2004 2006*Phase II trialsMS:8m 12.3mPhase III trial.1st line metastatic NSCLC NVB20Histology Matter of Navelbine.Histology Matter of Navelbine.21GLOB 3:GLOB 3:Patients characteristicsNVB I.V.30 mg/m D1*NVB Oral80 mg/m D8*CDDP80 mg/m D1(*1st cycle at 25 mg/m and 60 mg/m respectively)3-week cycles x6DCT75 mg/m D1CDDP75 mg/m D13-week cycles x6nMedian ageKPS 80-100Stage IVAdenoK/Squamous19459.4y.99.5%71%41.6%/34.1%19662.1y.100%76%39.3%/33.5%Drug deliveryMedian n of cyclesDose increased at cycle 24.2 cy71%71%4.4 cyNot applicableGLOB 3:Patients characteristicsTan,Ann Oncol 2009.GLOB 3:NVB I.V.30 mg/m D1*D2223GLOB 3:SurvivalNAVELBINE+CDDP versus docetaxel+CDDP:Similar OS NVBNVBTXTTXTP-value MS(m)9.929.82 0.66895%CI8.61 11.6 8.80 11.5HAZARD RATIO 0.948 0.744 1.209 Tan,Ann Oncol 2009.23GLOB 3:SurvivalNAVELBINE+23Histology highlights in metastatic settingGLOB 3:Adenocarcinoma outcome is improved by chemotherapies.Tan,Ann Oncol 2009GLOB 3 NVB Oral+CDDP armn=190ADK subtype41.6%ptsOther types58.4%ptsORMS29.1%11.7 m26.1%9.0m.Histology highlights in metast24CONCLUSIONSafety profile of Oral vinorelbine was qualitatively comparable to IV regimen.Oral vinorelbine(Navelbine)offers the convenience of an oral administration without interfering with the efficacy and the safety of the well-established IV vinorelbineHistology matter in Navelbine?.CONCLUSIONSafety profile of O25Navelbine in Maintenance Therapy.Navelbine in Maintenance Ther26271st line metastatic NSCLC-NAVELBINE Oral+CBDCA(1/2-Reck)Phase II trialNVB Oral 80*mg/m/week+CBDCA AUC5 D1 q3w Maintenance NVBo 80*cy 5-6(pts with OR or SD)ITT populationMedian ageMedian nb of cycles in combinationNumber of pts receiving maintenancen=5661 37-714 1-452.6%Dose escalation67.3%ORDCPFSMS1-YS17.9%73.2%4.3m9.7m37.1%*after testing myelosensitivity at 60 mg/m/week at the first 3 administrationsHigh efficacy of NAVELBINE Oral reproducing NVB I.V.dataReck,Lung Cancer 2009.271st line metastatic NSCLC-2728NAVELBINE Oral+CBDCA(2/2-Reck)Gr.3-4 toxicities(%of pts)NVB Oral+CBDCAMaintenance NVBoNeutropeniaFebrile neutropeniaThrombocytopeniaAnaemiaNausea/VomitingDiarrhoeaFatigue68%7.1%16%22%7%(Gr.3)/7%(Gr.3)4%(Gr.3)2(Gr.3)20%NR3.3%(Gr.3)6.6%0/03.3%(Gr.3)3.3%(Gr.3)The combination of NVB Oral+CBDCA“offers an active and safe regimen for patients with unresectable localized or metastatic NSCLC,for whom palliation coupled with optimal safety is the main end point.”Reck,Lung Cancer 2009.28NAVELBINE Oral+CBDCA(2/2 28Treatment of Special Populations:Elderly and PS2 patients.Treatment of Special Populatio29Randomized Trials in Elderly NSCLCTrialGroupCommentV vs BSCELVISCompletedGV vs VSICOGCompletedG vs V vs GVITA-MILESCompleted.Randomized Trials in Elderly N3030Chemotherapy in Elderly Patients with Advanced NSCLC13%4.576 15%Vinorelbine30%*776 22%Gemcitabine+VinorelbineFrasci14%4.976 -BSC32%*6.5 78 20%VinorelbineGridelli*1 YRMS(mo)N ResponseRegimenAuthor*Gridelli,J Natl Cancer Inst 1999;85:365-376.Frasci et al,Proc ASCO 2001,19:A1895*p0.05.Chemotherapy in Elderly Patien3131The MILES Phase III Trial:Gemcitabine+Vinorelbine vs Vinorelbine and vs Gemcitabine in Elderly Advanced NSCLC Patients NSCLC 70+years oldChemotherapy nave Stage IIIB(N3 or pleural effusion)or IVPS 0-2RANDOMIZEGridellii et al.ASCO 2001 Abstract 1230Vinorelbine 30 mg/m2 d1,8Q 3 weeksGemcitabine 1000 mg/m2 d1,8Vinorelbine 25 mg/m2 d1,8 Q 3 weeksGemcitabine 1200 mg/m2 d1,8Q 3 weeks.The MILES Phase III Trial:Gem3232Single Agent Chemotherapy in Elderly Patients with Advanced NSCLC*Gridelli,J Natl Cancer Inst 1999;85:365-376.Frasci et al,JCO 2000;18(13):2529-2536 Gridelli,J Natl Cancer Inst 2003;95:No5*p0.05Author Regimen N Response MS(mo)1 YR Vinorelbine 78 20%6.5 32%*BSC 76 -4.9 14%Gemcitabine+Vinorelbine 76 22%7 30%*Vinorelbine 76 15%4.5 13%Vinorelbine 233 18.4%8.8 41%Gemcitabine 233 17.3%6.6 26%Gemcitabine+Vinorelbine 237 20%7.6 31%Gridelli*FrasciGridelli 3333.Single Agent Chemotherapy in*3333NavelbineOral Navelbine vs.IV NavelbineOral Navelbine vs.IV Navelbine EfficacyEfficacy Quality of lifeQuality of life ConvenienceConvenienceAdjuvant chemotherapy with NavelbineAdjuvant chemotherapy with Navelbine Lace meta-analysisLace meta-analysisNavelbine in first line Navelbine in first line Histology matter?Histology matter?Navelbine in maintenance therapyNavelbine in maintenance therapyNavelbine in elderlyNavelbine in elderly MonotherapyMonotherapy.NavelbineOral Navelbine vs.IV3434