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Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC
Open accessAbstract
Introduction Although the interaction between tumor immune microenvironment and angiogenesis has been well established, evidence supporting the chemo-free combination of immune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors in treatment-naive patients with advanced NSCLC is insufficient. This report provides the efficacy and safety of sintilimab combined with anlotinib as first-line therapy for advanced NSCLC from a phase 1b trial (NCT03628521).Methods Eligible patients who were treatment-naive and had unresectable stage IIIB/C or IV NSCLC without EGFR/ALK/ROS1 mutations received sintilimab (200 mg, day 1) and anlotinib (12 mg, day 1-14) every 3 weeks till disease progression or unacceptable toxicity. Baseline programmed death-ligand 1 expression and tumor mutation burden status was assessed in all patients. The primary end points were objective response rate and safety.Results A total of 22 patients received sintilimab and anlotinib. Median follow-up was 15.8 months (range: 8.3-19.3). Sixteen patients achieved confirmed partial response with an objective response rate of 72.7% (95% confidence interval [CI]: 49.8%-89.3%) and disease control rate of 100% (95% CI: 84.6%-100%). Median progression-free survival was 15 months (95% CI: 8.3 m, not reached), and the 12-month progression-free survival rate was 71.4% (95% CI: 47.2%-86.0%). The incidence rate of grade 3 or higher treatment-related adverse events was 54.5%, and grade 3 hypertension was predominant (two of 22, 9.1%). No grade 4 treatment-related adverse events were observed, and one case of grade 5 immune-related pneumonitis occurred.Conclusions To the best of our knowledge, this is the first study that assessed an anti-programmed cell death protein 1 antibody combined with a multitarget antiangiogenic tyrosine kinase inhibitor in the frontline setting for patients with NSCLC. In view of its encouraging efficacy, durability, and safety profile, sintilimab plus anlotinib represents a novel chemotherapy-free regimen in this patient population.
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“Combination therapies such as sintilimab plus anlotinib, sintilimab plus IBI305 (bevacizumab biosimilar), camrelizumab plus apatinib, and toripalimab plus axitinib demonstrated potent antitumor effects in multiple types of cancers [22, 114–120].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [118]
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Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
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Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer
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Metadata
- Authors
- Chu, T., Zhong, R., Zhong, H., Zhang, B., Zhang, W., Shi, C., Qian, J., Zhang, Y., Chang, Q., Zhang, X., Dong, Y., Teng, J., Gao, Z., Qiang, H., Nie, W., Zhao, Y., Han, Y., Chen, Y., & Han, B.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Han, Baohui
- ORCID
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 16
- Issue
- 4
- Pages
- 643-652
- ISSN
- 1556-0864 (ISSN-L)
- OpenAlex
- W3126928179
- Cited by
- 227
- References
- 37
- Citations by year
- 2026: 11 · 2025: 35 · 2024: 56 · 2023: 53 · 2022: 54 · 2021: 17
- FWCI
- 16.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science and Technology Commission of Shanghai Municipality (18411968500)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- sintilimab, anlotinib, non-small cell lung cancer, first-line therapy, immune checkpoint inhibitors, antiangiogenic tyrosine kinase inhibitors, anti-PD-1 therapy, combination immunotherapy, chemotherapy-free regimen, tumor immune microenvironment, tumor angiogenesis, objective response rate, progression-free survival, treatment-related adverse events, hypertension, immune-related pneumonitis, PD-L1 expression
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Humans, Indoles, Lung Neoplasms, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Quinolines, Tumor Microenvironment, Antibodies, Monoclonal, Humanized
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