ICI Rechallenge With Anlotinib May Benefit Pretreated ES-SCLC

Patients whose extensive-stage small-cell lung cancer initially relapsed on prior lines of therapy with immune checkpoint inhibitors (ICI) may benefit from ICI rechallenge with anlotinib, according to data from a single-center, retrospective study published in Drug Design, Development and Therapy.

Data from the trial revealed that among 68 patients with ES-SCLC previously treated with ICI-based treatment who received anlotinib plus ICI therapy, the overall response rate (ORR) was 32.4% (95% CI, 21.5%-44.8%), composed entirely of partial responses. A total of 41.2% experienced stable disease, and 20.6% experienced disease progression, with an additional 5.9% not evaluable due to incomplete imaging assessments. The disease control rate (DCR) in this patient population was 73.5% (95% CI, 61.4%-83.5%).

Among responders (n = 22), the median duration of response (DOR) was 6.8 months (95% CI, 0.80-12.83) with a 12-month DOR rate of 40.4% (95% CI, 20.3%-59.8%) and a 20-month DOR rate of 30.3% (95% CI, 10.4%-53.3%). In the progression-free survival (PFS) analysis, 72.1% of patients experienced disease progression or death at data cutoff, with a median PFS of 5.6 months (95% CI, 3.87-7.33). The 12- and 24-month PFS rates were 30.9% (95% CI, 19.8%-42.7%) and 9.2% (95% CI, 1.0%-29.2%). Additionally, across 3 dose levels of anlotinib—8 mg, 10 mg, 12 mg––the median PFS was 3.0 months (95% CI, 1.54-4.46), 6.1 months (95% CI, 3.71-8.49), and 7.8 months (95% CI, 0.00-17.91), respectively (P = .136).

“Anlotinib plus ICIs demonstrated potential efficacy and manageable safety in patients with previously ICIs-treated ES-SCLC in clinical practice,” Teng-Fei Chen, researcher of the Department of Respiratory Medicine Ward at The First Affiliated Hospital of Zhengzhou University in Zhengzhou, China, wrote in the publication with study coinvestigators. “Immunotherapy rechallenge in previously ICI-treated ES-SCLC was feasible and of clinical significance preliminarily. Despite the encouraging results, further validation in larger, multi-center trials was needed to confirm the long-term efficacy and safety subsequently.”

Additional efficacy data revealed that after a median follow-up of 12.5 months (range, 1.1-31.5), 64.7% of patients had died, with a median overall survival (OS) of 13.2 months (95% CI, 7.09-19.31) for this patient group. The 24- and 30-month OS rates were both 27.6% (95% CI, 16.3%-40.2%).

The single-center, retrospective study included patients with ES-SCLC who relapsed following prior immunotherapy between September 2018 and September 2024. A total of 68 patients underwent at least 1 cycle of therapy with anlotinib plus ICI-based therapy, with anlotinib given at 8 to 12 mg once daily orally on a 2-week on and 1-week off schedule. ICI-based therapy included PD-1 inhibitors: tislelizumab (Tevimbra) at 200 mg or serplulimab (Hetronifly) at 4.5 mg/kg via intravenous infusion every 3 weeks; or PD-L1 inhibitors: atezolizumab (Tecentriq) at 1200 mg or adebrelimab (Ariely) at 20 mg/kg via intravenous infusion every 3 weeks.

Patients treated in the study had a median age of 61 years (range, 21-77), with 45.6% older than 61 years old. Seventy-five percent of patients were male, 77.9% had an ECOG performance score of 0 to 1, and 83.8% of patients were former smokers. Furthermore, 64.7% of patients received 2 or more prior lines of therapy, 69.1% were resistant to prior platinum-based treatment, and 19.1% received other systemic therapy between immunotherapy lines.

The primary end point of the study was OS. Secondary end points included ORR, DCR, PFS, and DOR.

Regarding safety, 89.7% of patients experienced treatment-related adverse effects (TRAEs), with 54.4% of patients experiencing grade 3 or higher TRAEs. The common TRAEs included fatigue (55.9%), nausea/vomiting (45.6%), hypertension (41.2%), hematologic toxicity (33.8%), liver function abnormality (26.5%), and anorexia (22.1%). Furthermore, the most common grade 3 or higher TRAEs included nausea/vomiting and hypertension (14.7% each), fatigue (13.3%), and liver function abnormality (11.8%).

No unexpected or grade 5 TRAEs were observed in the study. The safety profile of the combination therapy in patients with ES-SCLC who received previous immunotherapy-based treatment was found to be acceptable and manageable.

Reference

Chen T-F, Li Z-J, Zhao H-S, Yang R. Feasibility and safety of anlotinib combined with immune checkpoint inhibitors in patients with previously immunotherapy-treated extensive-stage small cell lung cancer: a retrospective exploratory study. Drug Des Devel Ther. 2025:19:4491-5005. doi:10.2147/DDDT.S525481