Immunotherapy combined with rh-endostatin improved clinical outcomes over immunotherapy plus chemotherapy for second-line treatment of advanced NSCLC

Background Despite the fact that numerous clinical and preclinical studies have demonstrated the synergistic effects of combining antiangiogenic or chemotherapy with immunotherapy, no data have been found to indicate that combination therapy is more effective and safer as second-line therapy. Methods We retrospectively compared the effectiveness and safety of ICIs plus rh-endostatin to ICIs plus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The evaluation indicators of this study were progression-free survival (PFS), safety profile, objective response rate (ORR), disease control rate (DCR), and 1-year overall survival (OS). Results The median PFS with immunotherapy plus rh-endostatin (IE) was 7.10 months (95% CI, 4.64 to 9.56) versus 5.13 months (95% CI, 4.29 to 5.97) with immunotherapy plus chemotherapy (IC) (HR, 0.56; 95%CI, 0.33 to 0.95). Treatment-related adverse events of grade 3 or 4 occurred in 7.5% of the IE group versus 25.0% of the IC group. The ORR in the IE group was 35.0% versus 20.8% in the IC group (P = 0.137), and the DCR in the IE group was 92.5% versus 77.1% in the IC group (P = 0.049). The 1-year OS rate for the IE group was 69.4%, which was higher than the 61.4% of the IC group. Conclusion Our study showed that ICI therapy combined with endostatin therapy exhibits high efficacy and safety, suggesting that such a combination might be a viable treatment option for patients with pre-treated NSCLC in the future.

[1]  Li-Yu Daisy Liu,et al.  Rh‐endostatin plus camrelizumab and chemotherapy in first‐line treatment of advanced non‐small cell lung cancer: A multicenter retrospective study , 2022, Cancer medicine.

[2]  M. Baine,et al.  The Association of Immunotherapy With the Overall Survival of Inoperable Stage III Non-small Cell Lung Cancer Patients Who Do Not Receive Chemoradiation , 2022, Journal of immunotherapy.

[3]  Peng Liu,et al.  Combined effects of programmed cell death-1 blockade and Endostar on brain metastases of lung cancer. , 2022, Anti-cancer agents in medicinal chemistry.

[4]  Yukiko Nakamura,et al.  A Randomized Comparison of Nivolumab versus Nivolumab + Docetaxel for Previously Treated Advanced or Recurrent ICI-Naïve Non–Small Cell Lung Cancer: TORG1630 , 2022, Clinical cancer research : an official journal of the American Association for Cancer Research.

[5]  X. Yan,et al.  Low-dose anlotinib confers improved survival in combination with immune checkpoint inhibitor in advanced non-small cell lung cancer patients , 2022, Cancer Immunology, Immunotherapy.

[6]  Yan-Hong Gao,et al.  Case Report: Recombinant Human Endostatin Plus Chemotherapy for Epidermal Growth Factor Receptor-Negative Miliary Lung Adenocarcinoma , 2022, Frontiers in Oncology.

[7]  Jae Jun Kim,et al.  Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small-cell lung cancer , 2021, Translational lung cancer research.

[8]  Ying Cheng,et al.  Camrelizumab plus carboplatin and paclitaxel as first-line treatment for advanced squamous non-small-cell lung cancer (CameL-sq): a phase 3 trial. , 2021, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[9]  P. Xing,et al.  Study protocol: A single‐arm, multicenter, phase II trial of camrelizumab plus apatinib for advanced nonsquamous NSCLC previously treated with first‐line immunotherapy , 2021, Thoracic cancer.

[10]  Ying Cheng,et al.  Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial. , 2020, The Lancet. Respiratory medicine.

[11]  B. Han,et al.  Phase Ib Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients with Advanced Non-small Cell Lung Cancer. , 2020, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[12]  Keunchil Park,et al.  Ramucirumab and durvalumab for previously treated, advanced non-small-cell lung cancer, gastric/gastro-oesophageal junction adenocarcinoma, or hepatocellular carcinoma: An open-label, phase Ia/b study (JVDJ). , 2020, European journal of cancer.

[13]  E. Ruíz-García,et al.  Editorial: Neovascularization, Angiogenesis and Vasculogenic Mimicry in Cancer , 2020, Frontiers in Oncology.

[14]  A. Tafreshi,et al.  A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer: Protocol-Specified Final Analysis of KEYNOTE-407. , 2020, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[15]  R. Rosell,et al.  Efficacy and Safety of Pembrolizumab Plus Docetaxel vs Docetaxel Alone in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer: The PROLUNG Phase 2 Randomized Clinical Trial. , 2020, JAMA oncology.

[16]  S. Novello,et al.  Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  B. Han,et al.  New advances in antiangiogenic combination therapeutic strategies for advanced non-small cell lung cancer , 2020, Journal of Cancer Research and Clinical Oncology.

[18]  R. Motzer,et al.  Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  Jin-liang Wang,et al.  Anti-PD-1 Therapy plus Chemotherapy and/or Bevacizumab as Second Line or later Treatment for Patients with Advanced Non-Small Cell Lung Cancer , 2020, Journal of Cancer.

[20]  Neovascularization, Angiogenesis and Vasculogenic Mimicry in Cancer , 2020, Frontiers Research Topics.

[21]  R. Herbst,et al.  Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial. , 2019, The Lancet. Oncology.

[22]  Y. Liu,et al.  Comparison of efficacy and toxicity of bevacizumab, endostar and apatinib in transgenic and human lung cancer xenograftzebrafish model , 2018, Scientific Reports.

[23]  J. Lunceford,et al.  Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy , 2018, Science.

[24]  Federico Cappuzzo,et al.  Atezolizumab for First‐Line Treatment of Metastatic Nonsquamous NSCLC , 2018, The New England journal of medicine.

[25]  A. Morabito Second-line treatment for advanced NSCLC without actionable mutations: is immunotherapy the ‘panacea’ for all patients? , 2018, BMC Medicine.

[26]  G. Zalcman,et al.  Bevacizumab in advanced lung cancer: state of the art. , 2017, Future oncology.

[27]  Bruno Larrivée,et al.  Tumor angiogenesis and vascular normalization: alternative therapeutic targets , 2017, Angiogenesis.

[28]  Carlos Barrios,et al.  Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial , 2017, The Lancet.

[29]  Edward S. Kim,et al.  Clinicopathologic Features of Advanced Squamous NSCLC. , 2016, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[30]  Y. Shentu,et al.  Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial , 2016, The Lancet.

[31]  C. Rudin,et al.  Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. , 2015, The New England journal of medicine.

[32]  L. Crinò,et al.  Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. , 2015, The New England journal of medicine.

[33]  J. Lunceford,et al.  Pembrolizumab for the treatment of non-small-cell lung cancer. , 2015, The New England journal of medicine.

[34]  Qiang Chen,et al.  Long‐term results of a randomized, double‐blind, and placebo‐controlled phase III trial: Endostar (rh‐endostatin) versus placebo in combination with vinorelbine and cisplatin in advanced non‐small cell lung cancer , 2013, Thoracic cancer.

[35]  R. Jain Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  C. Xu,et al.  Endostar, a modified endostatin inhibits non small cell lung cancer cell in vitro invasion through osteopontin-related mechanism. , 2009, European journal of pharmacology.

[37]  J. Geddes,et al.  What is a randomised controlled trial? , 2009, Epidemiologia e Psichiatria Sociale.

[38]  Markus Voelter,et al.  State of the Art , 1997, Pediatric Research.

[39]  Michael Schwenk,et al.  Tumor , 1828, The London medical and physical journal.

[40]  R. Guo,et al.  Camrelizumab Plus Carboplatin and Paclitaxel as First-Line Treatment for Advanced Squamous NSCLC (CameL-Sq): A Phase 3 Trial Study , 2022 .