Research progress of tumor vascular targeting drugs combined with PD-1/PD-L1 antibody in the treatment of digestive system tumors

doi:10.3760/cma.j.issn.1673-422X.2019.12.009

Abstract

Abstract: In recent years, tumor vascular targeting drugs and programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors have made great progress in tumor therapy. However, monotherapy not only has limited efficacy, but also has drug resistance. The results of many clinical trials at home and abroad showed that the combination of the two were used in the treatment of different tumors of digestive system, such as esophageal cancer, gastric cancer and gastroesophageal junction cancer, liver cancer and so on, so the combination of vascular targeting drugs and PD-1/PD-L1 antibody may be a breakthrough program in tumor therapy because of their good efficacy and safety.

Key words: Molecular targeted therapy, Angiogenesis inhibitors, Digestive system neoplasms, PD-1, PD-L1

Qi Ruili, Wang Huaqing. Research progress of tumor vascular targeting drugs combined with PD-1/PD-L1 antibody in the treatment of digestive system tumors[J]. Journal of International Oncology, 2019, 46(12): 750-754.

References ［34］

［1］	杜君, 郑荣寿, 庄建辉, 等. 我国食管癌疾病负担与国家自然科学基金基础研究资助情况的相关性分析［J］. 中国肿瘤, 2019, 28(4): 246-251. DOI: 10.11735/j.issn.1004-0242.2019.04.A002.
［2］	Ajani JA, Gerdes H, Bentrem DJ, et al. Esophageal and Esophagogastric Junction Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology［EB/OL］. ［2019-05-29］. https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf.
［3］	A phase Ⅰ/Ⅱ study of regorafenib plus avelumab in solid tumors (REGOMUNE)［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT03475953?term=NCT03475953&rank=1.
［4］	SHR-1210 in combination with apatinib and chemotherapy in patients with advanced esophageal squamous cell cancer［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT03603756?term=NCT03603756&rank=1.
［5］	Combination of chemotherapy plus RT and SHR-1210 to treat patients with ESCC［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT03671265?term=NCT03671265&rank=1.
［6］	孙可欣, 郑荣寿, 张思维, 等. 2015年中国分地区恶性肿瘤发病和死亡分析［J］. 中国肿瘤, 2019, 28(1): 1-11. DOI: 10.11735/j.issn.1004-0242.2019.01.A001.
［7］	Ajani JA, Farjah F, Bentrem DJ, et al. Gastric Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology［EB/OL］. ［2019-06-03］. https://www.nccn.org/professionals/physician_gls/pdf/Gastric.pdf.
［8］	Bang YJ, Golan T, Lin CC, et al. (2018) Interim safety and clinical activity in patients (pts) with locally advanced and unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma from a multicohort phase 1 study of ramucirumab (R) plus durvalumab (D)［J］. J Clin Oncol, 2018, 36(4): 92. DOI: 10.1200/JCO.2018.36.4_suppl.92.
［9］	Shah MA, Metges JP, Chun PY, et al. A phase Ⅱ, open-label, randomized study to evaluate the efficacy and safety of GS-5745 combined with nivolumab versus nivolumab alone in subjects with unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma［J］. J Clin Oncol, 2017, 35(15): TPS4141. DOI: 10.1200/JCO.2017.35.15_suppl.TPS4141.
［10］	A phase 1/2 study of ramucirumab plus nivolumab in participants with gastric or GEJ cancer［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT02999295?term=NCT02999295&rank=1.
［11］	A phase Ⅱ a study of lenvatinib, a multi-targeted tyrosine kinase inhibitor, combined with pembrolizumab (PD-1 inhibitor) for the treatment of metastatic gastroesophageal cancer patients who have progressed on first or subsequent line therapies［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT03321630?term=NCT03321630&rank=1.
［12］	徐琦, 应杰儿. 晚期原发性肝癌内科治疗进展［J］. 中国肿瘤, 2019, 28(5): 373-380. DOI: 10.11735/j.issn.1004-0242.2019.05.A010.
［13］	Ikeda M, Sung MW, Kudo M, et al. A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEM) in patients (pts) with unresectable hepatocellular carcinoma (uHCC)［J］. J Clin Oncol, 2018, 36(15_suppl): 4076. DOI: 10.1200/JCO.2018.36.15_suppl.4076.
［14］	Pishvaian MJ, Lee MS, Ryoo BY. Updated safety and clinical activity results from a phase Ⅰb study of atezolizumab + bevacizumab in hepatocellular carcinoma (HCC)［J］. Ann Oncol, 2018, 29 (8): LBA26. DOI: 10.1093/annonc/mdy424.028.
［15］	A study of atezolizumab in combination with bevacizumab compared with sorafenib in patients with untreated locally advanced or metastatic hepatocellular carcinoma ［IMbrave150］ (IMbrave150)［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT03434379?term=NCT03434379&rank=1.
［16］	Sorafenib tosylate and pembrolizumab in treating patients with advanced or metastatic liver cancer［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT03211416?term=NCT03211416&rank=1.
［17］	Safety and efficacy of lenvatinib (E7080/MK-7902) in combination with pembrolizumab (MK-3475) versus lenvatinib as first-line therapy in participants with advanced hepatocellular carcinoma (MK-7902-002/E7080-G000-311/LEAP-002)［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT03713593?term=NCT03713593&rank=1.
［18］	Seufferlein T, Mayerle J. Pancreatic cancer in 2015: precision medicine in pancreatic cancer-fact or fiction?［J］. Nat Rev Gastroenterol Hepatol, 2016, 13(2): 74-75. DOI: 10.1038/nrgastro.2015.215.
［19］	Adamska A, Domenichini A, Falasca M. Pancreatic ductal adenocarcinoma: current and evolving therapies［J］. Int J Mol Sci, 2017, 18(7). pii: E1338. DOI: 10.3390/ijms18071338.
［20］	Ioka T, Okusaka T, Ohkawa S, et al. Efficacy and safety of axitinib in combination with gemcitabine in advanced pancreatic cancer: subgroup analyses by region, including Japan, from the global randomized phase Ⅲ trial［J］. Jpn J Clin Oncol, 2015, 45(5): 439-448. DOI: 10.1093/jjco/hyv011.
［21］	Middleton G, Palmer DH, Greenhalf W, et al. Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial［J］. Lancet Oncol, 2017, 18(4): 486-499. DOI: 10.1016/S1470-2045(17)30084-0.
［22］	Sun D, Ma J, Wang J, et al. Clinical observation of immune checkpoint inhibitors in the treatment of advanced pancreatic cancer: a real-world study in Chinese cohort［J］. Ther Clin Risk Manag, 2018, 14: 1691-1700. DOI: 10.2147/TCRM.S173041.
［23］	Cappello P, Curcio C, Mandili G, et al. Next generation immunotherapy for pancreatic cancer: DNA vaccination is seeking new combo partners［J］. Cancers (Basel), 2018, 10(2). pii: E51. DOI: 10.3390/cancers10020051.
［24］	Jiang H, Hegde S, Knolhoff BL, et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy［J］. Nat Med, 2016, 22(8): 851-860. DOI: 10.1038/nm.4123.
［25］	Atezolizumab and bevacizumab in treating patients with rare solid tumors［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT03074513?term=NCT03074513&rank=1.
［26］	QUILT3.039: NANT pancreatic cancer vaccine: combination immunotherapy in subjects with pancreatic cancer who have progressed on or after standard-of-care therapy［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT03136406?term=NCT03136406&rank=1.
［27］	QUILT-3.088: NANT pancreatic cancer vaccine［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT03563144?term=NCT03563144&rank=1.
［28］	Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade［J］. Science, 2017, 357(6349): 409-413. DOI: 10.1126/science.aan6733.
［29］	Overman MJ, Mcdermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repairdeficient or microsatellite instability-high colorectal cancer (CheckMate142): an open-label, multicentre, phase 2 study［J］. Lancet Oncol, 2017, 18(9): 1182-1191. DOI: 10.1016/S1470-2045(17)30422-9.
［30］	Wallin J, Pishvaian MJ, Hernandez G, et al. Clinical activity and immune correlates from a phase Ⅰb study evaluating atezolizumab (anti-PDL1) in combination with FOLFOX and bevacizumab (anti-VEGF) in metastatic colorectal carcinoma［J］. Cancer Research, 2016, 76(14): 2651. DOI: 10.1158/1538-7445.AM2016-2651.
［31］	Hochster HS, Bendell JC, Cleary JM, et al. Efficacy and safety of atezolizumab (atezo) and bevacizumab (bev) in a phase Ⅰb study of microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC)［J］. J Clin Oncol, 2017, 35(4_suppl): 673. DOI: 10.1200/JCO.2017.35.4_suppl.673.
［32］	Grothey A, Tabernero J, Arnold D, et al. Fluoropyrimidine (FP)+ bevacizumab (BEV) + atezolizumab vs FP/BEV in BRAFwt metastatic colorectal cancer (mCRC): findings from cohort 2 of MODUL-a multicentre, randomized trial of biomarkerdriven maintenance treatment following first-line induction therapy［J］. Ann Oncol, 2018, 29(8): LBA19. DOI: 10.1093/annonc/mdw424.020.
［33］	Capecitabine and bevacizumab with or without atezolizumab in treating patients with refractory metastatic colorectal cancer［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT02873195?term=NCT02873195&rank=1.
［34］	Combination chemotherapy, bevacizumab, and/or atezolizumab in treating patients with deficient dna mismatch repair metastatic colorectal cancer［EB/OL］. ［2019-07-16］. https://www.clinicaltrials.gov/ct2/show/NCT02997228?term=NCT02997228& rank=1.

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