Anlotinib in combination with penpulimab and chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A single-arm, prospective clinical study.

e20136 Background: In recent years, the combination of immunotherapy and chemotherapy has emerged as a standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, these regimens generally offer a median progression-free survival (mPFS) of around 6 months and a median overall survival (mOS) of approximately 15 months, which does not provide a significant advantage over chemotherapy alone. Our previous study on the first-line treatment of ES-SCLC using anlotinib plus EP/EC regimen demonstrated a 9-months PFS and a 19-months OS. Unlike other PD-1 monoclonal antibodies based on the IgG4 subtype, Penpulimab is a novel PD-1 monoclonal antibody based on the IgG1 subtype, which prevents aggregation and avoids immune escape associated with IgG4 monoclonal antibodies. Therefore, we conducted a single-center study evaluating anlotinib combined with Penpulimab and the EP/EC regimen as a first-line treatment for ES-SCLC. Methods: ES - SCLC patients aged 18 to 80 years, not received any treatment, no significant cardiac, hepatic, or renal dysfunction. This regimen comprised Anlotinib Hydrochloride (10mg,QD, from day 1 to 14 of each 21-day cycle), Penpulimab (200md, on day 1 of each 21-day cycle), Etoposide (100 mg/m² on days 1-3 of each 21-day cycle), and either CBP (AUC=4-5 on day 1 every 3 weeks) or DDP (70-75 mg/m² on day 1 every 3 weeks). The combination therapy was administered for 4 to 6 cycles. Following this, maintenance therapy with Anlotinib Hydrochloride (10mg ,qd, from day 1 to 14 of each 21-day ) and Penpulimab (200 mg on day 1 of each 21-day) was continued until disease progression or the occurrence of an intolerable adverse reaction. If Anlotinib was not tolerated, its dose could be reduced to 8 mg. The primary endpoints of observation included objective response rate (ORR), PFS, OS, and adverse reactions (ADR). Results: Between March 6, 2021, and March 31, 2024, a total of 25 patients with ES-SCLC were enrolled in this study and completed the treatment regimen. The mean age of the patients was 65.0 ± 8.5 years (range: 45-80 years), with 18 males (72%) and 7 females (28%). The median PFS was 11.0 months (95% CI: 9.38-12.62), and the median OS was 23.0 months (95% CI: 15.66-30.34). The ORR was 90%, and the DCR was 100%. Grade 3 or higher adverse reactions included neutropenia in 15 patients (60%), thrombocytopenia in 10 patients (40%), nausea and vomiting in 7 patients (28%), anemia in 3 patients (12%), fatigue in 8 patients (32%), hypertension and elevated transaminase levels in 5 patients each (20%), and hoarseness in 1 patients (4%). Conclusions: The combination of Anlotinib with Penpulimab and EP/EC regimens, has demonstrated superior PFS, OS, ORR, and DCR in initial ES-SCLC treatments, with manageable adverse events. A randomized, controlled phase III clinical study will be conducted to further validate these promising results. Clinical trial information: ChiCTR2200065238 .