Research Progress of PD-1/PD-L1 Inhibitors in Patients with Recurrent or Metastatic Cervical Cancer

doi:10.12280/gjfckx.20211154

Abstract

Abstract:

Cervical cancer is the fourth leading cause of cancer-related deaths in women worldwide. The 5-year survival rate is only 17% for recurrent or metastatic cervical cancer, which impels clinicians to explore new treatment strategies. As an immunotherapy, PD-1/PD-L1 inhibitors have shown certain advantages in recurrent or metastatic cervical cancer, but the quality of clinical data needs to be further improved. Observations have shown the significant synergy of anti-angiogenesis agents, radiotherapy and chemotherapy with PD-1/PD-L1 inhibitors. For the purpose of the improved prognosis of patients with advanced cervical cancer, the team provides an overview of the theoretical basis and application status of PD-1/PD-L1 inhibitors in cervical cancer, as well as several clinical trials in combination with other treatment modes. The team also discusses the subsequent immune-related adverse events and the biomarkers for the evaluation of immunotherapy, so as to better manage adverse reactions and guide clinical medication.

Key words: Programmed cell death 1 receptor, Uterine cervical neoplasms, Neoplasm recurrence, local, Neoplasm metastasis, Antineoplastic protocols, Programmed death ligand-1

HAN Pin, WEN Jing, LIU Yu-chen, SUN Yi, WANG Yuan-pei, REN Fang. Research Progress of PD-1/PD-L1 Inhibitors in Patients with Recurrent or Metastatic Cervical Cancer[J]. Journal of International Obstetrics and Gynecology, 2022, 49(4): 393-397.

References 36

[1]	王玲, 王志莲. DKK3、Wnt/β-连环蛋白信号通路与宫颈癌关系的研究进展[J]. 国际妇产科学杂志, 2021, 48(5):539-542. doi: 10.12280/gjfckx.20201169. doi: 10.12280/gjfckx.20201169
[2]	Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3):209-249. doi: 10.3322/caac.21660. doi: 10.3322/caac.21660
[3]	苏雅婷, 吕杰, 牛雯娟, 等. PD-L1、B7-H3及B7-H4在宫颈癌免疫治疗中的研究进展[J]. 国际妇产科学杂志, 2021, 48(4):457-461. doi: 10.12280/gjfckx.20201027. doi: 10.12280/gjfckx.20201027
[4]	巨宇叶, 张芳芳, 王晓慧. 复发性宫颈癌的治疗现状及进展[J]. 国际妇产科学杂志, 2021, 48(1):56-60. doi: 10.12280/gjfckx.20200695. doi: 10.12280/gjfckx.20200695
[5]	He X, Xu C. Immune checkpoint signaling and cancer immunotherapy[J]. Cell Res, 2020, 30(8):660-669. doi: 10.1038/s41422-020-0343-4. doi: 10.1038/s41422-020-0343-4
[6]	Chen Y, Pei Y, Luo J, et al. Looking for the Optimal PD-1/PD-L1 Inhibitor in Cancer Treatment: A Comparison in Basic Structure, Function, and Clinical Practice[J]. Front Immunol, 2020, 11:1088. doi: 10.3389/fimmu.2020.01088. doi: 10.3389/fimmu.2020.01088 pmid: 32547566
[7]	Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer[J]. Am J Cancer Res, 2020, 10(3):727-742.
[8]	Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, et al. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2[J]. J Exp Med, 2012, 209(6):1201-1217. doi: 10.1084/jem.20112741. doi: 10.1084/jem.20112741
[9]	Topalian SL, Taube JM, Pardoll DM. Neoadjuvant checkpoint blockade for cancer immunotherapy[J]. Science, 2020, 367(6477):eaax0182. doi: 10.1126/science.aax0182. doi: 10.1126/science.aax0182
[10]	Patsoukis N, Brown J, Petkova V, et al. Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation[J]. Sci Signal, 2012, 5(230):ra46. doi: 10.1126/scisignal.2002796. doi: 10.1126/scisignal.2002796
[11]	Boussiotis VA. Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway[J]. N Engl J Med, 2016, 375(18):1767-1778. doi: 10.1056/NEJMra1514296. doi: 10.1056/NEJMra1514296
[12]	Allouch S, Malki A, Allouch A, et al. High-Risk HPV Oncoproteins and PD-1/PD-L1 Interplay in Human Cervical Cancer: Recent Evidence and Future Directions[J]. Front Oncol, 2020, 10:914. doi: 10.3389/fonc.2020.00914. doi: 10.3389/fonc.2020.00914
[13]	Liu C, Lu J, Tian H, et al. Increased expression of PD-L1 by the human papillomavirus 16 E7 oncoprotein inhibits anticancer immunity[J]. Mol Med Rep, 2017, 15(3):1063-1070. doi: 10.3892/mmr.2017.6102. doi: 10.3892/mmr.2017.6102
[14]	Chung HC, Ros W, Delord JP, et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study[J]. J Clin Oncol, 2019, 37(17):1470-1478. doi: 10.1200/JCO.18.01265. doi: 10.1200/JCO.18.01265
[15]	Naumann RW, Hollebecque A, Meyer T, et al. Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial[J]. J Clin Oncol, 2019, 37(31):2825-2834. doi: 10.1200/JCO.19.00739. doi: 10.1200/JCO.19.00739 pmid: 31487218
[16]	Yetkin-Arik B, Kastelein AW, Klaassen I, et al. Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy[J]. Biochim Biophys Acta Rev Cancer, 2021, 1875(1): 188446. doi: 10.1016/j.bbcan.2020.188446. doi: 10.1016/j.bbcan.2020.188446
[17]	Yi M, Jiao D, Qin S, et al. Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment[J]. Mol Cancer, 2019, 18(1):60. doi: 10.1186/s12943-019-0974-6. doi: 10.1186/s12943-019-0974-6
[18]	Lan C, Shen J, Wang Y, et al. Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial[J]. J Clin Oncol, 2020, 38(34):4095-4106. doi: 10.1200/JCO.20.01920. doi: 10.1200/JCO.20.01920
[19]	Galluzzi L, Humeau J, Buqué A, et al. Immunostimulation with chemotherapy in the era of Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm,immune checkpoint inhibitors[J]. Nat Rev Clin Oncol, 2020, 17(12):725-741. doi: 10.1038/s41571-020-0413-z. doi: 10.1038/s41571-020-0413-z
[20]	Lyu M, Shen Y, Beharee N, et al. The Combined Use of Chemotherapy and Radiotherapy with PD-1 Inhibitor, Pembrolizumab, in Advanced Cervical Cancer: A Case Report[J]. Onco Targets Ther, 2020, 13:4465-4471. doi: 10.2147/OTT.S245190. doi: 10.2147/OTT.S245190
[21]	Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer[J]. N Engl J Med, 2021, 385(20):1856-1867. doi: 10.1056/NEJMoa2112435. doi: 10.1056/NEJMoa2112435
[22]	MOLE RH. Whole body irradiation; radiobiology or medicine?[J]. Br J Radiol, 1953, 26(305):234-241. doi: 10.1259/0007-1285-26-305-234. doi: 10.1259/0007-1285-26-305-234
[23]	Brooks ED, Chang JY. Time to abandon single-site irradiation for inducing abscopal effects[J]. Nat Rev Clin Oncol, 2019, 16(2):123-135. doi: 10.1038/s41571-018-0119-7. doi: 10.1038/s41571-018-0119-7 pmid: 30401936
[24]	Lotfi N, Thome R, Rezaei N, et al. Roles of GM-CSF in the Pathogenesis of Autoimmune Diseases: An Update[J]. Front Immunol, 2019, 10:1265. doi: 10.3389/fimmu.2019.01265. doi: 10.3389/fimmu.2019.01265
[25]	Kelley RK, Mitchell E, Behr S, et al. Phase II trial of pembrolizumab (PEM) plus granulocyte macrophage colony stimulating factor (GM-CSF) in advanced biliary cancers (ABC)[J]. J Clin Oncol, 2018, 36(Suppl 4):386. doi: 10.1200/JCO.2018.36.15_suppl.4087. doi: 10.1200/JCO.2018.36.15_suppl.4087
[26]	Vilalta M, Brune J, Rafat M, et al. The role of granulocyte macrophage colony stimulating factor (GM-CSF) in radiation-induced tumor cell migration[J]. Clin Exp Metastasis, 2018, 35(4):247-254. doi: 10.1007/s10585-018-9877-y. doi: 10.1007/s10585-018-9877-y
[27]	Kong Y, Zhao X, Zou L, et al. PD-1 inhibitor combined with radiotherapy and GM-CSF as salvage therapy in patients with chemotherapy-refractory metastatic solid tumors[J]. J Clin Oncol, 2020, 38(Suppl 15):e15173. doi: 10.1200/JCO.2020.38.15_suppl.e15173. doi: 10.1200/JCO.2020.38.15_suppl.e15173
[28]	Youn JW, Hur SY, Woo JW, et al. Pembrolizumab plus GX-188E therapeutic DNA vaccine in patients with HPV-16-positive or HPV-18-positive advanced cervical cancer: interim results of a single-arm, phase 2 trial[J]. Lancet Oncol, 2020,21(12):1653-1660. doi: 10.1016/S1470-2045(20)30486-1. doi: 10.1016/S1470-2045(20)30486-1
[29]	Mayadev J, Nunes AT, Li M, et al. CALLA: Efficacy and safety of concurrent and adjuvant durvalumab with chemoradiotherapy versus chemoradiotherapy alone in women with locally advanced cervical cancer: a phase III, randomized, double-blind, multicenter study[J]. Int J Gynecol Cancer, 2020, 30(7):1065-1070. doi: 10.1136/ijgc-2019-001135. doi: 10.1136/ijgc-2019-001135 pmid: 32447296
[30]	Xu C, Chen YP, Du XJ, et al. Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis[J]. BMJ, 2018, 363:k4226. doi: 10.1136/bmj.k4226. doi: 10.1136/bmj.k4226
[31]	Ramos-Casals M, Brahmer JR, Callahan MK, et al. Immune-related adverse events of checkpoint inhibitors[J]. Nat Rev Dis Primers, 2020, 6(1):38. doi: 10.1038/s41572-020-0160-6. doi: 10.1038/s41572-020-0160-6 pmid: 32382051
[32]	Esfahani K, Elkrief A, Calabrese C, et al. Moving towards personalized treatments of immune-related adverse events[J]. Nat Rev Clin Oncol, 2020, 17(8):504-515. doi: 10.1038/s41571-020-0352-8. doi: 10.1038/s41571-020-0352-8
[33]	Ren D, Hua Y, Yu B, et al. Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy[J]. Mol Cancer, 2020, 19(1):19. doi: 10.1186/s12943-020-1144-6. doi: 10.1186/s12943-020-1144-6
[34]	Zhao P, Li L, Jiang X, et al. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy[J]. J Hematol Oncol, 2019, 12(1):54. doi: 10.1186/s13045-019-0738-1. doi: 10.1186/s13045-019-0738-1
[35]	Fumet JD, Truntzer C, Yarchoan M, et al. Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts[J]. Eur J Cancer, 2020, 131:40-50. doi: 10.1016/j.ejca.2020.02.038. doi: 10.1016/j.ejca.2020.02.038
[36]	Jiang X, Wu H, Zhao W, et al. Lycopene improves the efficiency of anti-PD-1 therapy via activating IFN signaling of lung cancer cells[J]. Cancer Cell Int, 2019, 19:68. doi: 10.1186/s12935-019-0789-y. doi: 10.1186/s12935-019-0789-y