Background: Combination of etoposide and cisplatin/carboplatin is the most commonly used initial chemoptherapy regiment in extensive-stage small cell lung cancer. A meta-analysis released that, there is no significant difference was observed in Objective response rate(ORR), progression-free survival (PFS), or overall survival(OS) in patients(pts) receiving cisplatin-base versus carboplatin-based regimens. We performed a single-arm phase II trial to determine if maintain of single-agent anlotinib, an oral VEGFR, FGFR, PDGFR and c-Kit tyrosine kinase inhibitor, after 4-6 cycles of anlotinib + etoposide + cisplatin/carboplatin would improve PFS and ORR. Methods: SCLC pts (18~70 yrs, extensive-stage SCLC, no prior systematic chemo/ICI therapy) received anlotinib( 12mg QD from day 1 to 14 of a 21-day cycle) +etoposide( 100mg/m², d1~3 of 21-day cycle)+ cisplatin( 75-80mg/m²,Q3W)/ carboplatin( AUC = 5~6,Q3W) for 4~6 cycles, and anlotinib maintenance. The dual-primary endpoint were PFS and ORR. Results: Between Oct.2018 to Dec.2019, 27 pts enrolled and included in the efficacy and safety analysis: age: median 62 (range:44-71); male 93%; cisplatin/ carboplatin/ both 11%/78%/11%; 37%(10/27) of pts required chemotherapy dose modification only, and the other 30% (8/27) of pts required anlotinib+ chemotherapy dose modification.The median PFS was 9.61 months ( 95%Cl:7.80-11.42). ORR was 77.78% (21/27), disease control rate (DCR) was 96.30% (26/27).Toxicities≥grade 3 included: neutropenia 22%, leukopenia 11%, hand-foot syndrome 15%, nausea 4%, mucositis 4%, edema 4%, anorexia 4%, xerostomia 4% and fatigue 4%; there were no grade 5 toxicities. Conclusions: Combined treatment with anlotinib plus etoposide and cisplatin/carboplatin for treatment-naive extensive-stage SCLC was well tolerated with promising PFS and ORR to date but showed no new risk for AEs. Based on these encouraging results, phase III trial of anlotinib plus etoposide and cisplatin/carboplatin for treatment-naive SCLC has been warranted.