Abstract
BACKGROUND: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma. METHODS: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations received a rational-based combination of camrelizumab (200 mg intravenously, day one), apatinib (250 mg, q.d., five continuous days per week), and nab-paclitaxel (135 mg/m(2) intravenously, days one and eight) every three weeks for four to six cycles in China. Patients with controlled disease were maintained with camrelizumab and apatinib. The primary end point was progression-free survival (PFS). This trial is registered with ClinicalTrials.gov (No. NCT04459078). FINDINGS: Between August 26, 2020 and May 20, 2022, 64 patients were enrolled. The median PFS was 14.3 (95% CI: 9.9, not reached) months. The confirmed objective response rate was 64.1% (95% CI: 51.1, 75.7). The grade 3-4 hematologic treatment-related adverse events (TRAEs) were decreased neutrophil count (14.1%), decreased white blood cell count (7.8%), and anemia (3.1%). The most common non-hematologic TRAEs of grade 3-4 were increased alanine transaminase (18.8%) and aspartate transaminase (15.6%). No treatment-related death occurred. The quality of life was on average not clinically meaningful worse through treatment cycle 14. INTERPRETATION: Nab-paclitaxel plus camrelizumab and apatinib showed clinically meaningful anti-tumor activity and manageable safety, with few hematologic toxicities, and might be a potential treatment option in patients with advanced lung adenocarcinoma lacking EGFR/ALK mutations. FUNDING: Heath Research Foundation of Chinese Society of Clinical Oncology, Hunan Provincial Natural Science Foundation of China, Hunan Cancer Hospital Climb Plan, Sister Institution Network Fund of The University of Texas MD Anderson Cancer Center, The Science and Technology Innovation Program of Hunan Province, and Suzhou Sheng Diya Biomedical Co., Ltd, a subsidiary of Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Shanghai, China).