Dataset Information

The Efficacy and Safety of Anlotinib Combined With PD-1 Antibody for Third-Line or Further-Line Treatment of Patients With Advanced Non-Small-Cell Lung Cancer.

ABSTRACT:

Background

Both anlotinib and programmed death 1 (PD-1) monoclonal antibody (mAb) have been approved for the third line treatment of metastatic non-small cell lung cancer (NSCLC). However, the combination of these two standard therapies has not been investigated in third-line or further-line treatment of patients with advanced NSCLC.

Methods

We reviewed 22 patients with NSCLC who received anlotinib combined with PD-1 mAb therapy from July 2018 to October 2019 at Sir Run Run Shaw Hospital. Based on the baseline characteristics, PD-L1 expression and EGFR mutation status, we retrospectively analyzed the efficacy and safety of this combination therapy by RESIST 1.1 and CTCAE 5.0.

Results

The combination treatment of anlotinib and PD-1 mAb in 22 NSCLC patients gained a median PFS of 6.8 months and a median OS of 17.3 months. The disease control rate (DCR) was 90.9%, and the objective response rate (ORR) was 36.4%, where 1 (4.6%) patient achieved complete response (CR) and 7 (31.8%) patients achieved partial response (PR). The median time to response was 3.9 months, and the median duration of the response was 6.8 months. The common grades 1-2 adverse events were fatigue 10/22 (45.5%), decreased appetite 9/22 (40.9%), hypertension 10/22 (45.5%); the common grades 3-4 adverse events were hypertension 2/22 (9.1%) and mouth ulceration 2/22 (9.1%).

Conclusion

Anlotinib combined with PD-1 mAb showed promising efficacy in third-line or further-line treatment of NSCLC, and its adverse effects is tolerable.

SUBMITTER: Zhai C

PROVIDER: S-EPMC7927598 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Efficacy and Safety of Anlotinib Combined With PD-1 Antibody for Third-Line or Further-Line Treatment of Patients With Advanced Non-Small-Cell Lung Cancer.

Zhai Chongya C Zhang Xiaoling X Ren Lulu L You Liangkun L Pan Qin Q Pan Hongming H Han Weidong W

Frontiers in oncology 20210217

<h4>Background</h4>Both anlotinib and programmed death 1 (PD-1) monoclonal antibody (mAb) have been approved for the third line treatment of metastatic non-small cell lung cancer (NSCLC). However, the combination of these two standard therapies has not been investigated in third-line or further-line treatment of patients with advanced NSCLC.<h4>Methods</h4>We reviewed 22 patients with NSCLC who received anlotinib combined with PD-1 mAb therapy from July 2018 to October 2019 at Sir Run Run Shaw H ...[more]

PMID: 33680942

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Project description:Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-Kit, and c-MET; therefore, it exhibits both antitumor and anti-angiogenetic activities. A phase III trial has shown that anlotinib improved progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC), who presented with progressive disease or intolerance after standard chemotherapy. This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment. Methods:Data were collected from March 2015 to January 2017 from a randomized, double-blind, placebo-controlled, multicenter, phase III trial of anlotinib (ALTER0303). A total of 437 patients were enrolled and randomly allocated (2:1) to the anlotinib and placebo groups. Kaplan-Meier analysis and log-rank test were performed to compare PFS and OS. Cox proportional hazards model was adopted for multivariate prognostic analysis. Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS. Meanwhile, elevated thyroid-stimulating hormone, blood glucose, and triglyceride levels; hypertension; and hand-foot syndrome were independent protective factors of PFS. High post-therapeutic peripheral blood granulocyte/lymphocyte ratio, an Eastern Cooperative Oncology Group (ECOG) score ? 2, and the sum of the maximal target lesion length at baseline were independent risk factors of OS, and hypertriglyceridemia was an independent protective factor of OS. Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC, and the baseline characteristics of the therapeutically dominant populations were then identified.

Project description:BackgroundThe evidence of combined therapies of multi-target agents in first-line treatment of advanced non-small cell lung cancer (NSCLC) was limited. This study aimed to evaluate the safety and efficacy of anlotinib combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), chemotherapy, or immune checkpoint inhibitor (ICI) in advanced NSCLC.MethodsThis open-label, three-arm, prospective study (NCT03628521) enrolled untreated locally advanced/metastatic NSCLC patients. Patients with EGFR mutation NSCLC received anlotinib and erlotinib (cohort A). Patients without EGFR/ALK/ROS1 mutation received anlotinib combined with carboplatin plus pemetrexed/gemcitabine (cohort B), or sintilimab (cohort C). The primary outcomes were safety and objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), disease control rate (DCR), and overall survival (OS). Treatments were performed for at least 2 cycles and efficacy was evaluated every 2 cycles using RECIST version 1.1. Safety was assessed throughout the study.ResultsA total of 30, 30, and 22 patients were enrolled in cohorts A, B, and C, respectively. There were 3 patients did not complete the treatment in cohort A. In cohorts A and B, ≥ grade 3 treatment-related adverse events (TRAEs) occurred in 77.3% and 60.0% of patients, respectively. The most common TRAEs were rash (10.0%) and decreased platelet count (30.0%) in cohorts A and B, respectively. The ORRs were 92.9% and 60.0% in cohorts A and B, respectively, and DCRs were 96.4% and 96.7%, respectively. The ORR and incidence of ≥ grade 3 TRAEs of cohort C were, which 72.7% and 54.5%, which had been published previously. Median PFSs [95% confidence interval (CI)] were 21.6 (15.6 to 24.9), 13.0 [10.5 to not estimated (NE)], and 15.6 (12.9 to NE) months in cohorts A, B, and C, respectively. Median OS was 28.1 (95% CI: 21.82 to NE) months in cohort B. The 24-month OS rates in cohorts A and C were 87.1% and 83.9%, respectively.ConclusionsAnlotinib-based combinations with EGFR-TKI, chemotherapy, and ICI are well-tolerated and encouraging as first-line therapies for advanced NSCLC, which could be verified in future studies. Anlotinib-based combination might provide multiple choices for first-line treatment in patients with advanced NSCLC.

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Dataset Information

The Efficacy and Safety of Anlotinib Combined With PD-1 Antibody for Third-Line or Further-Line Treatment of Patients With Advanced Non-Small-Cell Lung Cancer.

Background

Methods

Results

Conclusion

Publications

The Efficacy and Safety of Anlotinib Combined With PD-1 Antibody for Third-Line or Further-Line Treatment of Patients With Advanced Non-Small-Cell Lung Cancer.

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