Real-World Efficacy and Safety of Anlotinib With and Without Immunotherapy in Advanced Non-Small Cell Lung Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Aug 16

PMID 34395243

Citations 15

Authors

Qi Xiong

Boyu Qin

Lingli Xin

Bo Yang

Qi Song

Yu Wang

Sujie Zhang

Yi Hu

Affiliations

Soon will be listed here.

Abstract

Aims: Combination of anti-angiogenesis therapy and immunotherapy has showed synergistic effects in non-small cell lung cancer (NSCLC). The aim of this retrospective study was to investigate the efficacy and safety of anlotinib with and without immunotherapy in NSCLC.

Methods: Pathologically confirmed NSCLC patients (stage IIIB-IV) receiving anlotinib between November 2018 and February 2020 were enrolled for retrospective analysis. The outcomes and safety of overall patients were evaluated, and the efficacies of anlotinib plus immunotherapy and anlotinib alone was compared. The primary endpoint was progression-free survival (PFS).

Results: A total of 80 patients (median age: 62 years, range: 29-86 years) were included. Overall median PFS was 4.3 months (95% confidence interval (CI): 2.7-5.9 months). In univariate analysis, patients without mutation, previous EGFR target therapy, and brain metastasis had significantly longer PFS. Cox regression analysis showed that only brain metastasis was an independent predictor of PFS. The median PFS of patients receiving anlotinib plus immunotherapy was slightly longer than that of patients receiving anlotinib alone (4.2 3.1 months); however, the difference was not statistically significant. A tendency of longer median PFS was observed in patients with adenocarcinoma, wild type, stage IV, no liver metastasis, former smoker, ≥2 previous treatment lines, no previous VEGF or EGFR target therapies in anlotinib plus immunotherapy group. Treatments with anlotinib alone or anlotinib plus immunotherapy were well tolerable. The most common adverse events were fatigue, decreased hemoglobin count, hypertension, hand-foot syndrome, oral mucositis and hoarseness.

Conclusion: Anlotinib is well tolerable and effective in advanced NSCLC patients. Brain metastasis is an independent predictor of PFS in NSCLC patients receiving anlotinib. Future prospective studies with larger sample size and extended follow-up are needed to confirm the clinical benefit in NSCLC patients treated with anlotinib combined with immunotherapy.

Citing Articles

Clinical effectiveness of Anlotinib combined with PD-1 inhibitors in treating advanced non-small-cell lung carcinoma.

Han Z, Liu W, Wang F Am J Transl Res. 2025; 17(1):674-684.

PMID: 39959242 PMC: 11826207. DOI: 10.62347/WKFJ4968.

Efficacy and Safety of Anlotinib in EGFR-Positive Patients with Advanced Lung Adenocarcinoma Compared with Chemotherapy: A Retrospective Study.

Cai C, Shen Q, Shao J, Qu J, Zhou S, Zhou J Technol Cancer Res Treat. 2024; 23:15330338241279111.

PMID: 39175430 PMC: 11342426. DOI: 10.1177/15330338241279111.

Synergistic effect of additional anlotinib and immunotherapy as second-line or later-line treatment in pancreatic cancer: A retrospective cohort study.

Qin B, Xiong Q, Xin L, Li K, Shi W, Song Q Cancer Innov. 2024; 3(4):e123.

PMID: 38948252 PMC: 11212301. DOI: 10.1002/cai2.123.

Efficacy and safety of anlotinib in combination with immune checkpoint inhibitors or not as advanced non-small cell lung cancer treatment: a systematic review and network meta-analysis.

Wu Z, Zhou P, Zhao Y, Wang J, Gao S Transl Cancer Res. 2024; 13(5):2451-2463.

PMID: 38881944 PMC: 11170544. DOI: 10.21037/tcr-23-1483.

Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway.

Mao Q, Wang X, Lin F, Yu M, Fan H, Zheng Q Chin J Integr Med. 2024; 30(9):799-808.

PMID: 38850481 DOI: 10.1007/s11655-024-3803-8.

References

Shao L, Wang W, Song Z, Zhang Y . The efficacy and safety of anlotinib treatment for advanced lung cancer. Onco Targets Ther. 2019; 12:6549-6554. PMC: 6699585. DOI: 10.2147/OTT.S205674. View

Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z . Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2018; 4(11):1569-1575. PMC: 6248083. DOI: 10.1001/jamaoncol.2018.3039. View

Taurin S, Yang C, Reyes M, Cho S, Coombs D, Jarboe E . Endometrial Cancers Harboring Mutated Fibroblast Growth Factor Receptor 2 Protein Are Successfully Treated With a New Small Tyrosine Kinase Inhibitor in an Orthotopic Mouse Model. Int J Gynecol Cancer. 2017; 28(1):152-160. PMC: 5735020. DOI: 10.1097/IGC.0000000000001129. View

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J . Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018; 379(21):2040-2051. DOI: 10.1056/NEJMoa1810865. View

Hanna N, Kaiser R, Sullivan R, Aren O, Ahn M, Tiangco B . Nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with relapsed or refractory, advanced non-small cell lung cancer (LUME-Lung 2): A randomized, double-blind, phase III trial. Lung Cancer. 2016; 102:65-73. DOI: 10.1016/j.lungcan.2016.10.011. View

Wang L, He Z, Yang S, Tang H, Wu Y, Li S . The impact of previous therapy strategy on the efficiency of anlotinib hydrochloride as a third-line treatment on patients with advanced non-small cell lung cancer (NSCLC): a subgroup analysis of ALTER0303 trial. Transl Lung Cancer Res. 2019; 8(5):575-583. PMC: 6835105. DOI: 10.21037/tlcr.2019.09.21. View

Tumeh P, Hellmann M, Hamid O, Tsai K, Loo K, Gubens M . Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC. Cancer Immunol Res. 2017; 5(5):417-424. PMC: 5749922. DOI: 10.1158/2326-6066.CIR-16-0325. View

Wang P, Fang X, Yin T, Tian H, Yu J, Teng F . Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non-Small-Cell Lung Cancer After Previous Systemic Treatment Failure-A Retrospective Study. Front Oncol. 2021; 11:628124. PMC: 8005709. DOI: 10.3389/fonc.2021.628124. View

10.

Wang H, Chu J, Zhao Y, Tang H, Wang L, Zhou M . A Trial of the Safety and Efficacy of Chemotherapy Plus Anlotinib vs Chemotherapy Alone as Second- or Third-Line Salvage Treatment for Advanced Non-Small Cell Lung Cancer. Cancer Manag Res. 2020; 12:3827-3834. PMC: 7250176. DOI: 10.2147/CMAR.S249678. View

11.

Reck M, Kaiser R, Mellemgaard A, Douillard J, Orlov S, Krzakowski M . Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014; 15(2):143-55. DOI: 10.1016/S1470-2045(13)70586-2. View

12.

Brahmer J, Reckamp K, Baas P, Crino L, Eberhardt W, Poddubskaya E . Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(2):123-35. PMC: 4681400. DOI: 10.1056/NEJMoa1504627. View

13.

Paz-Ares L, Hirsh V, Zhang L, de Marinis F, Yang J, Wakelee H . Monotherapy Administration of Sorafenib in Patients With Non-Small Cell Lung Cancer (MISSION) Trial: A Phase III, Multicenter, Placebo-Controlled Trial of Sorafenib in Patients with Relapsed or Refractory Predominantly Nonsquamous Non-Small-Cell.... J Thorac Oncol. 2016; 10(12):1745-53. DOI: 10.1097/JTO.0000000000000693. View

14.

Zhou C, Wu Y, Chen G, Liu X, Zhu Y, Lu S . BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2015; 33(19):2197-204. DOI: 10.1200/JCO.2014.59.4424. View

15.

Lian Z, Du W, Zhang Y, Fu Y, Liu T, Wang A . Anlotinib can overcome acquired resistance to EGFR-TKIs via FGFR1 signaling in non-small cell lung cancer without harboring EGFR T790M mutation. Thorac Cancer. 2020; 11(7):1934-1943. PMC: 7327692. DOI: 10.1111/1759-7714.13485. View

16.

Shin D, Na I, Kim C, Park S, Baek H, Yang S . EGFR mutation and brain metastasis in pulmonary adenocarcinomas. J Thorac Oncol. 2014; 9(2):195-9. DOI: 10.1097/JTO.0000000000000069. View

17.

Li H, Xu Y, Wan B, Song Y, Zhan P, Hu Y . The clinicopathological and prognostic significance of PD-L1 expression assessed by immunohistochemistry in lung cancer: a meta-analysis of 50 studies with 11,383 patients. Transl Lung Cancer Res. 2019; 8(4):429-449. PMC: 6749117. DOI: 10.21037/tlcr.2019.08.04. View

18.

Wu D, Nie J, Dai L, Hu W, Zhang J, Chen X . Salvage treatment with anlotinib for advanced non-small cell lung cancer. Thorac Cancer. 2019; 10(7):1590-1596. PMC: 6610258. DOI: 10.1111/1759-7714.13120. View

19.

Manegold C, Dingemans A, Gray J, Nakagawa K, Nicolson M, Peters S . The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC. J Thorac Oncol. 2016; 12(2):194-207. DOI: 10.1016/j.jtho.2016.10.003. View

20.

Topalian S, Sznol M, Mcdermott D, Kluger H, Carvajal R, Sharfman W . Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014; 32(10):1020-30. PMC: 4811023. DOI: 10.1200/JCO.2013.53.0105. View