Sintilimab plus anlotinib as second or further-line therapy for extensive disease small cell lung cancer: a phase 2 investigator-initiated non-randomized controlled trial

Background Treatment options remain rather limited for extensive disease small cell lung cancer (ED-SCLC) patients in second or further -line setting. Methods The phase 2 investigator -initiated non -randomized study enrolled patients who had disease progression on at least one line of platinum -based chemotherapy. Participants received intravenous sintilimab 200 mg on day one and oral daily anlotinib 12 mg on days 1 - 14 once every three weeks per cycle. The primary endpoint was progression -free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. This study is registered with ClinicalTrials.gov (NCT04055792). Findings Forty-two patients were enrolled between August 29, 2019 and December 26, 2021 at Henan Cancer Hospital in China. 37 patients were evaluable for ef fi cacy. The median follow-up was 24.8 months (IQR: 16.9 - 28.2). The median PFS was 6.1 months (95% CI: 5.0 - 7.3). The OS was 12.7 months (95% CI: 7.1 - 18.2). The ORR was 56.8% (21/37, 95% CI: 40.0 - 73.5) and the DCR was 89.2% (33/37, 95% CI: 78.7 - 99.7). Forty patients (40/42, 95%) had at least one treatment -related adverse event (TRAE). Immune -related adverse events (irAEs) were reported in 39 patients (39/42, 93%), while grade 3 or higher irAEs occurred in 11 patients (11/42, 26%). The most frequent irAEs were hypothyroidism (16/42, 38%), elevated gamma-glutamyl transpeptidase (15/42, 36%) and elevated creatine kinase MB (15/42, 36%). The most frequent grade 3 or higher irAEs were elevated gammaglutamyl transpeptidase (5/42, 12%) and increased aspartate aminotransferase (3/42, 7%). Interpretation Sintilimab plus anlotinib demonstrated promising antitumor activities as second or further -line therapy for ED-SCLC and had manageable toxicities. The fi ndings support further randomized controlled trials of this combination regimen for ED-SCLC.