Background: In recent years, the therapeutic regimens of extensive-stage small cell lung cancer (ES-SCLC) have progressed a lot. The most significant clinical studies include IMpower133 and CASPIAN. However, the relevant results showed that the combination of PD-L1 monoclonal antibody and EC regimen chemotherapy as first-line treatment of small cell lung cancer have a median PFS (progession-free survival) of about 5 months, which is comparable to that of simple chemotherapy. Therefore, the EP/EC is still the standard treatment for extensive-stage small cell lung cancer. Meanwhile, we noticed that anlotinib (multi-target small molecule oral VEGF inhibitor) has a curative effect on patients with extensive-stage SCLC as a third-line or above treatment in the ALTER 1202 study in China. Therefore, we tried to add anlotinib to the first-line treatment with EP/EC regimen in patients with ES-SCLC to observe the efficacy and safety. Methods: Eligible ES-SCLC pts (18̃75 years old, initial treatment, no obvious heart, liver and kidney dysfunction) were received anlotinib (12mg QD from day 1 to 14 of a 21-day cycle) + etoposide(100mg/m², d1̃3 of a 21-day cycle)+CBP (AUC = 4̃5,d1,Q3W) or DDP (70̃75mg/m², d1,Q3W) for 4̃6 cycles, then anlotinib maintenance (12mg QD from day 1 to 14 of a 21-day cycle) until the disease progresses or intolerable adverse reactions occur. During the treatment, dose reduction of anlotinib was permitted, which could be reduced to 10mg or 8mg if it was intolerable. The main observation endpoints were ORR, PFS and adverse events. Results: Between January 2019 and August 2020, a total of 20 patients with extensive-stage SCLC were enrolled in the study, with an average age of 66.2 ± 8.1(45-75) years old, 17 males (85%) and 3 females (15%). The median PFS was 10 months (95% CI: 7.809-12.191), median OS was 15 months (95%CI:10.639-19.361), ORR (objective remission rate) was 90% and DCR (disease control rate) was 100%. The most common grade 3 or 4 adverse events related to the trial regimen included: neutropenia was 10/20 (50.0%), thrombocytopenia was 5/20 (25.0%), anemia, nausea and fatigue were all 2/20 (10%), hypertension, transaminase elevation and hoarseness were all 1/20 (5%). Conclusions: Anlotinib combined with EP/EC regimen has better PFS, OS, ORR and DCR for the initial treatment of extensive-stage SCLC, and a manageable safety profile. A randomized, controlled phase III clinical study will be conducted to confirm this conclusion. Clinical trial information: ChiCTR2000035043.