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Background: PemC and PCB are regimens used for first-line treatment of advanced NS-NSCLC.The primary objective was to compare progression-free survival without Grade 4 toxicity(G4PFS)between two vs three drug regimen arms.Methods: Patients ≥18 years,Stage IV NS NSCLC,AJCC(v7.0),and ECOG PS 0/1 were enrolled.Patients were randomized(1:1); received 4 cycles of induction(PemC: Pem,500 mg/m2 and C,AUC = 6; PCB: P,200 mg/m2,C,AUC = 6,and B,15 mg/kg)followed by Pem(PemC Arm)or B(PCB Arm)maintenance therapy in the absence of progressive disease or discontinuation.Secondary endpoints were PFS,overall survival(OS),overall response rate(ORR),and disease control rate(DCR).The study was powered for G4PFS; assuming hazard ratio(HR)of 0.75; there was 80%power to detect superiority of PemC over PCB with a 2-sided type I error of 0.10.Efficacy data were analyzed by intent-to-treat principle using the log-rank test for time-to-event variables,and an exact test for ORR and DCR.Safety data were evaluated using CTCAE v3 for patients who received ≥1 dose of study treatment.Results: Patients were randomized to PemC(N = 182)or PCB(N = 179).Baseline factors were balanced between arms: median age 66/66 years;%female 42/42;%PS=0,47/47;%stage Ⅳ M1a 29/30; for PemC vs PCB,median G4PFS(months)was 3.91/2.86(HR = 0.85,90%CI 0.7,1.04,p = 0.176); PFS and OS had HR = 1.06(95%CI 0.84,1.35),p = 0.610,and HR = 1.07(95%CI 0.83,1.36),p = 0.616,respectively.The ORR(%)23.6/27.4 and DCR(%)59.9/57.0 were for PemC vs PCB,respectively.Significantly more drug-related grade 3/4 anemia(18.7%vs 5.4%),and thrombocytopenia(24.0%vs 9.6%)were seen on PemC; significantly more grade 3/4 neutropenia(48.8%vs 24.6%)and grade 1/2 alopecia(28.3%vs 8.2%)were seen on PCB.Conclusions: PemC was not superior to PCB in G4PFS; no difference in PFS or OS was observed for the two-vs three-drug regimens.There were no unexpected toxicities; the toxicity profiles demonstrated distinctions by arm,and both regimens demonstrated tolerability.