PD-(L)1 inhibitors plus anlotinib: A superior option for second-line treatment of extensive-stage small cell lung cancer.

e20117 Background: To evaluate the efficacy of PD-(L)1 inhibitors plus anlotinib as the second-line therapy of extensive-stage small cell lung cancer (ES-SCLC) in the real-world. Methods: EL-SCLC (n = 389) patients who received second-line treatment at 3 cancer centers between January 2008 and January 2023 were retrospectively analyzed. All patients received PD-(L)1 inhibitors in combination with anlotinib and/or chemotherapy(I+A±C), or PD-(L)1 inhibitors in combination with chemotherapy(I+C), or chemotherapy alone (C) as the second-line therapy. The efficacy including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), as well as safety were compared among three groups. Results: The baseline clinical characteristics among 3 groups were largely balanced. Compared with I+C (ORR=17.6%, DCR=68.8%) and C (ORR=18.0%, DCR=53.9%), I+A±C treatment had significantly higher ORR (30.2%) and DCR (82.6%). In addition, treatment with I+A±C generated the longest mPFS (7.2 months) and mOS (33.5 months) compared to that with I+C (mPFS=4.6 months, mOS=19.0 months, both P < 0.001) or C (mPFS=3.4 months, P < 0.01; mOS=18.3 months, P=0.083). However, addition of chemotherapy upon I+A did’t impact PFS (7.2 vs. 7.1 months, P=0.431) and OS (NA vs. 33.5 months, P=0.598). Stratified analysis showed that patients with female gender and oligometastasis (≤ 3 metastasis sites) benefit more from I+A±C treatment compared to male patients and those with polymetastasis, respectively. In addition, the combination of anlotinib with PD-L1 inhibitors generated superior PFS compared to that with PD-1 inhibitors. In patients not receiving PD-(L)1 inhibitors in first-line therapy, I+A±C treatment showed better PFS. The incidence of ≥ grade 3 myelosuppression is much lower in I+A±C group than those in I+C and C groups (3.5% vs 11.2% vs 16.3%, P < 0.01). However, I+A±C treatment generated a higher prevalence of immune-related pneumonia (2.3% vs 0% vs 0%, P < 0.05) and hemoptysis (1.4% vs 0% vs 0.6%, P < 0.05) compared with I+C and C. Conclusions: PD-(L)1 inhibitors plus anlotinib and/or chemotherapy has promising efficacy and manageable toxicity as second-line therpay of ES-SCLC.