Skip to main content
SpringerLink
Log in

Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup analysis of a randomized phase 2 study (ALTER1202)

  • Research Article
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ⩾ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gammaglutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Yang S, Zhang Z, Wang Q. Emerging therapies for small cell lung cancer. J Hematol Oncol 2019; 12(1): 47

    Article  PubMed  PubMed Central  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70(1): 7–30

    Article  PubMed  Google Scholar 

  3. Rudin CM, Giaccone G, Ismaila N. Treatment of small-cell lung cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline. J Oncol Pract 2016; 12(1): 83–86

    Article  PubMed  Google Scholar 

  4. Früh M, De Ruysscher D, Popat S, Crinò L, Peters S, Felip E; ESMO Guidelines Working Group. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi99–vi105

    Article  PubMed  Google Scholar 

  5. Zimmerman S, Das A, Wang S, Julian R, Gandhi L, Wolf J. 2017–2018 scientific advances in thoracic oncology: small cell lung cancer. J Thorac Oncol 2019; 14(5): 768–783

    Article  CAS  PubMed  Google Scholar 

  6. Ito T, Kudoh S, Ichimura T, Fujino K, Hassan WA, Udaka N. Small cell lung cancer, an epithelial to mesenchymal transition (EMT)-like cancer: significance of inactive Notch signaling and expression of achaete-scute complex homologue 1. Hum Cell 2017; 30(1): 1–10

    Article  PubMed  Google Scholar 

  7. Waqar SN, Morgensztern D. Treatment advances in small cell lung cancer (SCLC). Pharmacol Ther 2017; 180: 16–23

    Article  CAS  PubMed  Google Scholar 

  8. MacCallum C, Gillenwater HH. Second-line treatment of small-cell lung cancer. Curr Oncol Rep 2006; 8(4): 258–264

    Article  CAS  PubMed  Google Scholar 

  9. von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999; 17(2): 658–667

    Article  CAS  PubMed  Google Scholar 

  10. Ardizzoni A, Tiseo M, Boni L. Validation of standard definition of sensitive versus refractory relapsed small cell lung cancer: a pooled analysis of topotecan second-line trials. Eur J Cancer 2014; 50(13): 2211–2218

    Article  PubMed  Google Scholar 

  11. Asai N, Ohkuni Y, Kaneko N, Yamaguchi E, Kubo A. Relapsed small cell lung cancer: treatment options and latest developments. Ther Adv Med Oncol 2014; 6(2): 69–82

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ready N, Farago AF, de Braud F, Atmaca A, Hellmann MD, Schneider JG, Spigel DR, Moreno V, Chau I, Hann CL, Eder JP, Steele NL, Pieters A, Fairchild J, Antonia SJ. Third-line nivolumab monotherapy in recurrent SCLC: CheckMate 032. J Thorac Oncol 2019; 14(2): 237–244

    Article  CAS  PubMed  Google Scholar 

  13. Chung HC, Piha-Paul SA, Lopez-Martin J, Schellens JHM, Kao S, Miller WH Jr, Delord JP, Gao B, Planchard D, Gottfried M, Zer A, Jalal SI, Penel N, Mehnert JM, Matos I, Bennouna J, Kim DW, Xu L, Krishnan S, Norwood K, Ott PA. Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: results from the KEYNOTE-028 and KEYNOTE-158 Studies. J Thorac Oncol 2020; 15(4): 618–627

    Article  CAS  PubMed  Google Scholar 

  14. Xie C, Wan X, Quan H, Zheng M, Fu L, Li Y, Lou L. Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor. Cancer Sci 2018; 109(4): 1207–1219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shen G, Zheng F, Ren D, Du F, Dong Q, Wang Z, Zhao F, Ahmad R, Zhao J. Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development. J Hematol Oncol 2018; 11(1): 120

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chen D, Xu J, Zhao Y, Chu T, Zhong H, Han B, Zhong R. Prognostic value of tumor cavitation in extensive-stage small-cell lung cancer patients treated with anlotinib. J Cancer Res Clin Oncol 2020; 146(2): 401–406

    Article  CAS  PubMed  Google Scholar 

  17. Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z, Cheng Y, He J, Shi Y, Zhao Y, Yu H, Zhao Y, Chen W, Luo Y, Wu L, Wang X, Pirker R, Nan K, Jin F, Dong J, Li B, Sun Y. 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

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cheng Y, Wang Q, Li K, Shi J, Liu Y, Wu L, Han B, Chen G, He J, Wang J, Lou D, Yu H, Wang S, Qin H, Li X. Anlotinib vs placebo as third- or further-line treatment for patients with small cell lung cancer: a randomised, double-blind, placebo-controlled phase 2 study. Br J Cancer 2021; 125(3): 366–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cheng Y, Wang Q, Li K, Shi J, Wu L, Han B, Chen G, He J, Wang J, Qin H, Li X. OA13.03 Anlotinib as third-line or further-line treatment in relapsed SCLC: a multicentre, randomized, double-blind phase 2 trial. J Thorac Oncol 2018; 13(10): S351–S352

    Article  Google Scholar 

  20. Kim YH, Mishima M. Second-line chemotherapy for small-cell lung cancer (SCLC). Cancer Treat Rev 2011; 37(2): 143–150

    Article  PubMed  Google Scholar 

  21. Simos D, Sajjady G, Sergi M, Liew MS, Califano R, Ho C, Leighl N, White S, Summers Y, Petrcich W, Wheatley-Price P. Third-line chemotherapy in small-cell lung cancer: an international analysis. Clin Lung Cancer 2014; 15(2): 110–118

    Article  CAS  PubMed  Google Scholar 

  22. Pietanza MC, Kadota K, Huberman K, Sima CS, Fiore JJ, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Chan TA, Rizvi NA, Azzoli CG, Riely GJ, Kris MG, Krug LM. Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res 2012; 18(4): 1138–1145

    Article  CAS  PubMed  Google Scholar 

  23. Morgensztern D, Besse B, Greillier L, Santana-Davila R, Ready N, Hann CL, Glisson BS, Farago AF, Dowlati A, Rudin CM, Le Moulec S, Lally S, Yalamanchili S, Wolf J, Govindan R, Carbone DP. Efficacy and safety of rovalpituzumab tesirine in third-line and beyond patients with DLL3-expressing, relapsed/refractory small-cell lung cancer: results from the phase II TRINITY study. Clin Cancer Res 2019; 25(23): 6958–6966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, Antonia SJ, Ascierto PA, Moreno V, Atmaca A, Salvagni S, Taylor M, Amin A, Camidge DR, Horn L, Calvo E, Li A, Lin WH, Callahan MK, Spigel DR. Nivolumab monotherapy and nivolumab plus ipilimumab in recurrent small cell lung cancer: results from the CheckMate 032 randomized cohort. J Thorac Oncol 2020; 15(3): 426–435

    Article  CAS  PubMed  Google Scholar 

  25. Han B, Li K, Zhao Y, Li B, Cheng Y, Zhou J, Lu Y, Shi Y, Wang Z, Jiang L, Luo Y, Zhang Y, Huang C, Li Q, Wu G. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer 2018; 118(5): 654–661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wu D, Nie J, Hu W, Dai L, Zhang J, Chen X, Ma X, Tian G, Han J, Han S, Long J, Wang Y, Zhang Z, Fang J. A phase II study of anlotinib in 45 patients with relapsed small cell lung cancer. Int J Cancer 2020; 147(12): 3453–3460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors wish to thank all the participating patients and their families, study personnel at all sites, and the ALTER 1202 clinical trial team. This study was supported by the Jilin Provincial Health and Family Planning Commission (No. 2019J077), the Science and Technology Agency of Jilin Provincial Project (No. 20200201518JC), and Chia-tai Tianqing Pharmaceutical Group Co., Ltd. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Linyi Cancer Hospital, Linyi, 276002, China

    Jianhua Shi

  2. Department of Thoracic Medical Oncology, Jilin Cancer Hospital, Changchun, 130012, China

    Ying Cheng

  3. Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450003, China

    Qiming Wang

  4. Department of Pulmonary Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Kai Li

  5. Department of Thoracic Medical Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University (Hunan Cancer Hospital), Changsha, 410031, China

    Lin Wu

  6. Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China

    Baohui Han

  7. Department of Respiratory Medicine, Harbin Medical University Cancer Hospital, Harbin, 150081, China

    Gongyan Chen

  8. Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China

    Jianxing He

  9. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Jie Wang

  10. Department of Pulmonary Oncology, The Fifth Medical Centre of Chinese PLA General Hospital, Beijing, 100039, China

    Haifeng Qin

  11. Department of Medical Oncology, Liaoning Cancer Hospital, Shenyang, 110042, China

    Xiaoling Li

Authors
  1. Jianhua Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiming Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kai Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Baohui Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gongyan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jianxing He
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Haifeng Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xiaoling Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ying Cheng.

Ethics declarations

Jianhua Shi, Ying Cheng, Qiming Wang, Kai Li, Lin Wu, Baohui Han, Gongyan Chen, Jianxing He, Jie Wang, Haifeng Qin, and Xiaoling Li declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shi, J., Cheng, Y., Wang, Q. et al. Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup analysis of a randomized phase 2 study (ALTER1202). Front. Med. 16, 766–772 (2022). https://doi.org/10.1007/s11684-021-0916-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-021-0916-8

Keywords

Search

Navigation