Intervention
toxicity, PD, death, SD
DISEASE PROGRESSION, DISEASE, REMISSION, ADVERSE EFFECTS
All patients underwent baseline imaging assessment after enrollment. The participants started treatment within 3 weeks (21 calendar days) from screening. All participants were administered anlotinib plus etoposide. Specifically, all participants were treated with oral anlotinib 12 mg q.d. on days 1–14 of 21-day cycles. Three weeks (21 d) were considered as one cycle. Anlotinib was continually administered until disease progression, consent withdrawal, or intolerable toxicity. The participants were also treated with oral etoposide 50 mg on days 1 to 14 of 21-day cycles. Etoposide treatment lasted for six cycles maximum.During treatment, imaging examinations were performed every 2 cycles to assess clinical efficacy according to RECIST 1.1 criteria, including complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). Safety were evaluated every 3 weeks (21 ± 7 days) until disease progression, consent withdrawal, loss to follow-up, or intolerable toxicity. In case of disease progression, the participants were included in the survival follow-up phase, in which follow-up was performed every 56 ± 7 days until death, loss to follow-up, or consent withdrawal. Anti-tumor therapy after disease progression was decided by the investigators. Follow-up was recommended, and patient data were recorded.Medication was discontinued in case of disease progression. In case of grade 3 or 4 adverse effects, the oral dose of anlotinib was lowered to the next dose level. In patients using a starting dose of 12 mg/day, 10 mg/day and then 8 mg/day were subsequently used. If the initial dose was 10 mg/day, it was lowered to 8 mg/day. No dose lowering was allowed after 8 mg/d; in such cases requiring dose adjustment, treatment discontinuation was applied. When the initial dose was 8 mg/day, treatment discontinuation was directly applied if dose adjustment was necessary.