Consolidation thoracic radiotherapy following quadruple induction with benmelstobart, anlotinib, and chemotherapy for extensive-stage small cell lung cancer: rationale and protocol of a phase II study.

内容摘要

Extensive-stage small cell lung cancer (ES-SCLC) remains a highly aggressive malignancy with limited survival outcomes. While first-line immune checkpoint inhibitors combined with platinum-based chemotherapy have improved survival, the benefit is modest. Emerging evidence supports the integration of anti-angiogenic therapy and thoracic radiotherapy (TRT) to enhance systemic and local control. However, a comprehensive multimodal regimen combining chemotherapy, immunotherapy, anti-angiogenic therapy, and TRT has not been systematically evaluated. This study aims to assess the safety, feasibility, and preliminary efficacy of a multimodal treatment strategy involving induction with benmelstobart [an anti-programmed death-ligand 1 (PD-L1) antibody], platinum-etoposide chemotherapy, and anlotinib, followed by consolidation with benmelstobart, anlotinib, and sequential TRT in patients with untreated ES-SCLC. This is a prospective, single-center, single-arm, phase II, open-label trial conducted at Tianjin Medical University Cancer Institute & Hospital. Twenty-five patients with histologically confirmed, treatment-naive ES-SCLC and measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 will be enrolled. The regimen consists of-induction phase: 4 cycles of benmelstobart (1,200 mg IV q21d), carboplatin (area under the curve 5) or cisplatin (75-80 mg/m2) on day 1, etoposide (100 mg/m2 IV days 1-3), and oral anlotinib (12 mg once daily, 2 weeks on/1 week off); consolidation phase: 2 cycles of benmelstobart, anlotinib, and TRT (25 Gy in 5 daily fractions of 5 Gy each, administered only during the first consolidation cycle); maintenance phase: benmelstobart plus anlotinib until progression, unacceptable toxicity, or clinical deterioration. The co-primary endpoints are progression-free survival (PFS) and incidence of grade ≥3 treatment-related adverse events (TRAEs). Secondary endpoints include objective response rate and overall survival. Safety will be evaluated in all treated patients. This trial will provide critical preliminary evidence on the safety, feasibility, and efficacy of integrating short-course TRT into a quadruple chemo-immuno-antiangiogenic backbone for ES-SCLC. The results are expected to inform the design of future multicenter, randomized phase III trials and potentially establish a novel multimodal paradigm for first-line management. ClinicalTrials.gov identifier: NCT07358676. Protocol version: version 1.0, April 03, 2025.