PARP Inhibitors Combined with Immune Checkpoint Inhibitors in the Treatment of Gynecological Malignant Tumors

doi:10.12280/gjfckx.20240102

Abstract

Abstract:

In recent years the progress of targeted therapy and immunotherapy has developed rapidly, such as poly (ADP-ribose) polymerase inhibitor (PARPi) and immune checkpoint inhibitors (ICI) have changed the traditional treatment pattern of gynecologic tumors, but some patients have limited efficacy or develop drug resistance. Preclinical studies have found that PARPi damages DNA repair process, results in increasing tumor mutation burden and tumor -specific antigen neoantigens, modulates the tumor microenvironment, and stimulates the production of tumor infiltrating lymphocytes (TIL) and promotes anti-tumor immune response, which providing a theoretical basis for the combination treatment of PARPi and ICI. Recently, many clinical studies have found that the combination of PARPi and ICI can significantly improve the prognosis of patients with gynecological malignant tumors.

Key words: Genital neoplasms, female, Ovarian neoplasms, Endometrial neoplasms, Poly(ADP-ribose) polymerase inhibitors, Immune checkpoint inhibitors, Therapy

ZHOU Lin, YUAN Lin, WAN Yi-cong, ZHANG Lin, CHENG Wen-jun, JIANG Yi. PARP Inhibitors Combined with Immune Checkpoint Inhibitors in the Treatment of Gynecological Malignant Tumors[J]. Journal of International Obstetrics and Gynecology, 2024, 51(2): 206-209.

References 32

[1]	Zheng R, Zhang S, Zeng H, et al. Cancer incidence and mortality in China, 2016[J]. J Nati Cancer Cent, 2022, 2(1):1-9. doi: 10.1016/j.jncc.2022.02.002.
[2]	Moore K, Colombo N, Scambia G, et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer[J]. N Engl J Med, 2018, 379(26):2495-2505. doi: 10.1056/NEJMoa1810858.
[3]	Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer[J]. N Engl J Med, 2016, 375(22):2154-2164. doi: 10.1056/NEJMoa1611310.
[4]	Lau CH, Seow KM, Chen KH. The Molecular Mechanisms of Actions, Effects, and Clinical Implications of PARP Inhibitors in Epithelial Ovarian Cancers: A Systematic Review[J]. Int J Mol Sci, 2022, 23(15):8125. doi: 10.3390/ijms23158125.
[5]	Caracciolo D, Riillo C, Di Martino MT, et al. Alternative Non-Homologous End-Joining: Error-Prone DNA Repair as Cancer′s Achilles′ Heel[J]. Cancers(Basel), 2021, 13(6):1392. doi: 10.3390/cancers13061392.
[6]	Jiang X, Li X, Li W, et al. PARP inhibitors in ovarian cancer: Sensitivity prediction and resistance mechanisms[J]. J Cell Mol Med, 2019, 23(4):2303-2313. doi: 10.1111/jcmm.14133. pmid: 30672100
[7]	Watts FZ. Repair of DNA Double-Strand Breaks in Heterochromatin[J]. Biomolecules, 2016, 6(4):47. doi: 10.3390/biom6040047.
[8]	Naimi A, Mohammed RN, Raji A, et al. Tumor immunotherapies by immune checkpoint inhibitors(ICIs); the pros and cons[J]. Cell Commun Signal, 2022, 20(1):44. doi: 10.1186/s12964-022-00854-y. pmid: 35392976
[9]	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.
[10]	Kaushik I, Ramachandran S, Zabel C, et al. The evolutionary legacy of immune checkpoint inhibitors[J]. Semin Cancer Biol, 2022, 86(Pt 2):491-498. doi: 10.1016/j.semcancer.2022.03.020.
[11]	Catalano M, Francesco Iannone L, Cosso F, et al. Combining inhibition of immune checkpoints and PARP: rationale and perspectives in cancer treatment[J]. Expert Opin Ther Targets, 2022, 26(11):923-936. doi: 10.1080/14728222.2022.2158813.
[12]	Wanderley C, Correa TS, Scaranti M, et al. Targeting PARP1 to Enhance Anticancer Checkpoint Immunotherapy Response: Rationale and Clinical Implications[J]. Front Immunol, 2022, 13:816642. doi: 10.3389/fimmu.2022.816642.
[13]	Wu Z, Cui P, Tao H, et al. The Synergistic Effect of PARP Inhibitors and Immune Checkpoint Inhibitors[J]. Clin Med Insights Oncol, 2021, 15:1179554921996288. doi: 10.1177/1179554921996288.
[14]	Shen J, Zhao W, Ju Z, et al. PARPi Triggers the STING-Dependent Immune Response and Enhances the Therapeutic Efficacy of Immune Checkpoint Blockade Independent of BRCAness[J]. Cancer Res, 2019, 79(2):311-319. doi: 10.1158/0008-5472.CAN-18-1003. pmid: 30482774
[15]	Higuchi T, Flies DB, Marjon NA, et al. CTLA-4 Blockade Synergizes Therapeutically with PARP Inhibition in BRCA1-Deficient Ovarian Cancer[J]. Cancer Immunol Res, 2015, 3(11):1257-1268. doi: 10.1158/2326-6066.CIR-15-0044. pmid: 26138335
[16]	Wang Z, Sun K, Xiao Y, et al. Niraparib activates interferon signaling and potentiates anti-PD-1 antibody efficacy in tumor models[J]. Sci Rep, 2019, 9(1):1853. doi: 10.1038/s41598-019-38534-6.
[17]	Drew Y, Jonge M, Hong SH, et al. An open-label, phase Ⅱ basket study of olaparib and durvalumab (MEDIOLA): Results in germline BRCA -mutated (gBRCAm) platinum-sensitive relapsed (PSR) ovarian cancer (OC)[J]. Gynecol Oncol, 2018, 149:246-247. doi: 10.1016/j.ygyno.2018.04.555.
[18]	Banerjee S, Imbimbo M, Roxburgh P, et al. 529MO PhaseⅡstudy of olaparib plus durvalumab with or without bevacizumab (MEDIOLA): Final analysis of overall survival in patients with non-germline BRCA-mutated platinum-sensitive relapsed ovarian cancer[J]. Ann Onco, 2022, 33(Suppl 7):S788-S789. doi: 10.1016/j.annonc.2022.07.657.
[19]	Drew Y, Kaufman B, Banerjee S, et al. 1190PD - Phase Ⅱ study of olaparib + durvalumab (MEDIOLA): Updated results in germline BRCA-mutated platinum-sensitive relapsed (PSR) ovarian cancer (OC)[J]. Ann,Oncol, 2019, 30(Suppl 5):v485-v486. doi: 10.1093/annonc/mdz253.016.
[20]	Yap TA, Bardia A, Dvorkin M, et al. Avelumab Plus Talazoparib in Patients With Advanced Solid Tumors: The JAVELIN PARP Medley Nonrandomized Controlled Trial[J]. JAMA Oncol, 2023, 9(1):40-50. doi: 10.1001/jamaoncol.2022.5228.
[21]	Friedlander M, Mileshkin L, Lombard J, et al. Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase Ⅰ trial[J]. Br J Cancer, 2023, 129(5):797-810. doi: 10.1038/s41416-023-02349-0.
[22]	Wu X, Zhu J, Wang J, et al. Pamiparib Monotherapy for Patients with Germline BRCA1/2-Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, PhaseⅡStudy[J]. Clin Cancer Res, 2022, 28(4):653-661. doi: 10.1158/1078-0432.CCR-21-1186.
[23]	Pignata S, Pisano C, Di Napoli M, et al. Treatment of recurrent epithelial ovarian cancer[J]. Cancer, 2019, 125(Suppl 24):4609-4615. doi: 10.1002/cncr.32500.
[24]	Lee JM, Annunziata CM, Houston N, et al. A phase Ⅱ study of durvalumab, a PD-L1 inhibitor and olaparib in recurrent ovarian cancer (OvCa)[J]. Ann Oncol, 2018, 29(Suppl 8):viii334. doi: 10.1093/annonc/mdy285.145.
[25]	Kim YN, Joung JG, Park E, et al. Randomized, two-arm, noncomparative phase 2 study of olaparib plus cediranib or durvalumab in HRR-mutated, platinum-resistant ovarian cancer: A substudy of KGOG 3045[J]. Int J Cancer, 2023, 153(12):2032-2044. doi: 10.1002/ijc.34696.
[26]	Konstantinopoulos PA, Waggoner S, Vidal GA, et al. Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma[J]. JAMA Oncol, 2019, 5(8):1141-1149. doi: 10.1001/jamaoncol.2019.1048.
[27]	Pirš B, Škof E, Smrkolj V, et al. Overview of Immune Checkpoint Inhibitors in Gynecological Cancer Treatment[J]. Cancers(Basel), 2022, 14(3):631. doi: 10.3390/cancers14030631.
[28]	Kok PS, Antill YC, Scott CL, et al. The impact of single agent PD-1 or PD-L1 inhibition on advanced endometrial cancers: meta-analysis[J]. ESMO Open, 2022, 7(6):100635. doi: 10.1016/j.esmoop.2022.100635.
[29]	Makker V, Taylor MH, Aghajanian C, et al. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer[J]. J Clin Oncol, 2020, 38(26):2981-2992. doi: 10.1200/JCO.19.02627. pmid: 32167863
[30]	Post C, Westermann AM, Boere IA, et al. Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer(phase Ⅱ DOMEC trial)[J]. Gynecol Oncol, 2022, 165(2):223-229. doi: 10.1016/j.ygyno.2022.02.025.
[31]	Madariaga A, Garg S, Tchrakian N, et al. Clinical outcome and biomarker assessments of a multi-centre phase Ⅱ trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma[J]. Nat Commun, 2023, 14(1):1452. doi: 10.1038/s41467-023-37084-w. pmid: 36922497
[32]	Konstantinopoulos PA, Gockley AA, Xiong N, et al. Evaluation of Treatment With Talazoparib and Avelumab in Patients With Recurrent Mismatch Repair Proficient Endometrial Cancer[J]. JAMA Oncol, 2022, 8(9):1317-1322. doi: 10.1001/jamaoncol.2022.2181.