Phase II study of anlotinib plus durvalumab and chemotherapy as first-line treatment in extensive-stage small cell lung cancer (ES-SCLC): Efficacy and safety analysis.

e20131 Background: The combination of PD-L1 Checkpoint inhibitor and chemotherapy has revolutionized the first-line standard of care of ES-SCLC, yet the prognosis still need to be improved. In this phase 2 study, we aimed to enhance the patients benefit by adding anlotinib to durvalumab and chemotherapy, assessing its efficacy and safety. Methods: Eligible treatment naïve ES-SCLC patients, aged 18-75 years, were enrolled. Anlotinib + durvalumab + etoposide + carboplatin or cisplatin was administered for 4-6 cycles, followed by anlotinib and durvalumab maintenance until disease progression or intolerable toxicity. During the treatment, dose reduction of anlotinib was permitted, which could be reduced to 10mg or 8mg if it was intolerable. The primary endpoint is overall objective response rate (ORR), secondary endpoints are PFS and safety. Results: Between December 2020 and June 2022, 22 patients with extensive-stage SCLC were enrolled, including 8 patients (36.4%) with brain metastases and 11 patients (50%) with liver metastases. The median age was (39-73) years, 15 patients were males (68.2%). ORR was 100%, with 27.3% complete response rate (CR). The median PFS of all patients was 8.51months, and the PFS of patients with liver metastasis and brain metastasis were 9.43 months and 8.51 months respectively. The median OS was not reached. The most common grade ≥3 TEAEs ( > 10% incidence) included neutropenia and leukopenia (each 16.7%, 2/22), no new safety signals were observed. No grade 5 AE occurred. Conclusions: Durvalumab plus anlotinib and chemotherapy demonstrated promising PFS, ORR and manageable safety profile for the first-line treatment of ES-SCLC. Clinical trial information: NCT04660097 .