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PARP抑制剂在卵巢癌维持治疗中的研究进展
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Abstract:
卵巢癌是妇科疾病中预后最差的恶性肿瘤，由于早期症状不典型、缺乏特异性，所以早期诊断困难。初始治疗后复发率高，5年总生存率仅为40%，晚期卵巢癌的治疗成为临床工作中的难题。近年来，PARP抑制剂的应用，极大地改善了卵巢癌患者的生存期时间。PARP抑制剂作为一种新型的靶向治疗药物，在卵巢癌的维持治疗中取得了显著进展。本文对PARP抑制剂在卵巢癌维持治疗中的作用机制、临床研究、安全性等方面的研究进展进行综述，旨在为卵巢癌的临床治疗提供参考。
Ovarian cancer is a malignant tumor with the worst prognosis in gynecological diseases, and early diagnosis is difficult because of the untypical early symptoms and lack of specificity. The recurrence rate after initial treatment is high, the 5-year overall survival rate is only 40%, and the treatment of advanced ovarian cancer has become a difficult problem in clinical work. In recent years, the application of PARP inhibitors has greatly improved the survival time of ovarian cancer patients. As a new type of targeted therapy, PARP inhibitors have made remarkable progress in the maintenance therapy of ovarian cancer. In this paper, the research progress of the mechanism of action, clinical research and safety of PARP inhibitors in the maintenance treatment of ovarian cancer is reviewed, aiming to provide a reference for the clinical treatment of ovarian cancer.
| [1] | Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. https://doi.org/10.3322/caac.21660 |
| [2] | Xia, L., Peng, J., Lou, G., Pan, M., Zhou, Q., Hu, W., et al. (2022) Antitumor Activity and Safety of Camrelizumab plus Famitinib in Patients with Platinum-Resistant Recurrent Ovarian Cancer: Results from an Open-Label, Multicenter Phase 2 Basket Study. Journal for ImmunoTherapy of Cancer, 10, e003831. https://doi.org/10.1136/jitc-2021-003831 |
| [3] | 常鑫, 韩璐. 铂敏感复发性卵巢癌维持治疗药物的研究进展[J]. 国际妇产科学杂志, 2022, 49(4): 382-387. |
| [4] | Farmer, H., McCabe, N., Lord, C.J., Tutt, A.N.J., Johnson, D.A., Richardson, T.B., et al. (2005) Targeting the DNA Repair Defect in BRCA Mutant Cells as a Therapeutic Strategy. Nature, 434, 917-921. https://doi.org/10.1038/nature03445 |
| [5] | Bryant, H.E., Schultz, N., Thomas, H.D., Parker, K.M., Flower, D., Lopez, E., et al. (2005) Specific Killing of BRCA2-Deficient Tumours with Inhibitors of Poly (ADP-Ribose) Polymerase. Nature, 434, 913-917. https://doi.org/10.1038/nature03443 |
| [6] | DiSilvestro, P., Banerjee, S., Colombo, N., Scambia, G., Kim, B., Oaknin, A., et al. (2023) Overall Survival with Maintenance Olaparib at a 7-Year Follow-Up in Patients with Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. Journal of Clinical Oncology, 41, 609-617. https://doi.org/10.1200/jco.22.01549 |
| [7] | Bisch, S.P., Jago, C.A., Kalogera, E., Ganshorn, H., Meyer, L.A., Ramirez, P.T., et al. (2021) Outcomes of Enhanced Recovery after Surgery (ERAS) in Gynecologic Oncology—A Systematic Review and Meta-Analysis. Gynecologic Oncology, 161, 46-55. https://doi.org/10.1016/j.ygyno.2020.12.035 |
| [8] | Lorusso, D., Mouret-Reynier, M., Harter, P., Cropet, C., Caballero, C., Wolfrum-Ristau, P., et al. (2024) Updated Progression-Free Survival and Final Overall Survival with Maintenance Olaparib plus Bevacizumab According to Clinical Risk in Patients with Newly Diagnosed Advanced Ovarian Cancer in the Phase III PAOLA-1/ENGOT-Ov25 Trial. International Journal of Gynecological Cancer, 34, 550-558. https://doi.org/10.1136/ijgc-2023-004995 |
| [9] | Poveda, A., Floquet, A., Ledermann, J.A., Asher, R., Penson, R.T., Oza, A.M., et al. (2021) Olaparib Tablets as Maintenance Therapy in Patients with Platinum-Sensitive Relapsed Ovarian Cancer and a BRCA1/2 Mutation (SOLO2/ENGOT-Ov21): A Final Analysis of a Double-Blind, Randomised, Placebo-Controlled, Phase 3 Trial. The Lancet Oncology, 22, 620-631. https://doi.org/10.1016/s1470-2045(21)00073-5 |
| [10] | González-Martín, A., Pothuri, B., Vergote, I., DePont Christensen, R., Graybill, W., Mirza, M.R., et al. (2019) Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine, 381, 2391-2402. https://doi.org/10.1056/nejmoa1910962 |
| [11] | Li, N., Zhu, J., Yin, R., Wang, J., Pan, L., Kong, B., et al. (2023) Treatment with Niraparib Maintenance Therapy in Patients with Newly Diagnosed Advanced Ovarian Cancer. JAMA Oncology, 9, 1230-1237. https://doi.org/10.1001/jamaoncol.2023.2283 |
| [12] | Mirza, M.R., Monk, B.J., Herrstedt, J., Oza, A.M., Mahner, S., Redondo, A., et al. (2016) Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. New England Journal of Medicine, 375, 2154-2164. https://doi.org/10.1056/nejmoa1611310 |
| [13] | Wu, X.H., Zhu, J.Q., Yin, R.T., Yang, J.X., Liu, J.H., Wang, J., et al. (2021) Niraparib Maintenance Therapy in Patients with Platinum-Sensitive Recurrent Ovarian Cancer Using an Individualized Starting Dose (NORA): A Randomized, Double-Blind, Placebo-Controlled Phase III Trial. Annals of Oncology, 32, 512-521. https://doi.org/10.1016/j.annonc.2020.12.018 |
| [14] | Li, N., Bu, H., Liu, J., Zhu, J., Zhou, Q., Wang, L., et al. (2021) An Open-Label, Multicenter, Single-Arm, Phase II Study of Fluzoparib in Patients with Germline BRCA1/2 Mutation and Platinum-Sensitive Recurrent Ovarian Cancer. Clinical Cancer Research, 27, 2452-2458. https://doi.org/10.1158/1078-0432.ccr-20-3546 |
| [15] | Li, N., Zhang, Y., Wang, J., Zhu, J., Wang, L., Wu, X., et al. (2022) Fuzuloparib Maintenance Therapy in Patients with Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial. Journal of Clinical Oncology, 40, 2436-2446. https://doi.org/10.1200/jco.21.01511 |
| [16] | Mateo, J., Lord, C.J., Serra, V., Tutt, A., Balmaña, J., Castroviejo-Bermejo, M., et al. (2019) A Decade of Clinical Development of PARP Inhibitors in Perspective. Annals of Oncology, 30, 1437-1447. https://doi.org/10.1093/annonc/mdz192 |
| [17] | Wu, X., Zhu, J., Wang, J., Lin, Z., Yin, R., Sun, W., et al. (2021) Pamiparib Monotherapy for Patients with Germline BRCA1/2-Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study. Clinical Cancer Research, 28, 653-661. https://doi.org/10.1158/1078-0432.ccr-21-1186 |
| [18] | Markham, A. (2021) Pamiparib: First Approval. Drugs, 81, 1343-1348. https://doi.org/10.1007/s40265-021-01552-8 |
| [19] | Kaufman, B., Shapira-Frommer, R., Schmutzler, R.K., Audeh, M.W., Friedlander, M., Balmaña, J., et al. (2015) Olaparib Monotherapy in Patients with Advanced Cancer and a Germline BRCA1/2 Mutation. Journal of Clinical Oncology, 33, 244-250. https://doi.org/10.1200/jco.2014.56.2728 |
| [20] | Moore, K.N., Secord, A.A., Geller, M.A., Miller, D.S., Cloven, N., Fleming, G.F., et al. (2019) Niraparib Monotherapy for Late-Line Treatment of Ovarian Cancer (QUADRA): A Multi-Centre, Open-Label, Single-Arm, Phase 2 Trial. The Lancet Oncology, 20, 636-648. https://doi.org/10.1016/s1470-2045(19)30029-4 |
| [21] | Coleman, R.L., Sill, M.W., Bell-McGuinn, K., Aghajanian, C., Gray, H.J., Tewari, K.S., et al. (2015) A Phase II Evaluation of the Potent, Highly Selective PARP Inhibitor Veliparib in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Patients Who Carry a Germline BRCA1 or BRCA2 Mutation—An NRG Oncology/Gynecologic Oncology Group Study. Gynecologic Oncology, 137, 386-391. https://doi.org/10.1016/j.ygyno.2015.03.042 |
| [22] | Bai, P. (2015) Biology of Poly (ADP-Ribose) Polymerases: The Factotums of Cell Maintenance. Molecular Cell, 58, 947-958. https://doi.org/10.1016/j.molcel.2015.01.034 |
| [23] | Swisher, E.M., Lin, K.K., Oza, A.M., Scott, C.L., Giordano, H., Sun, J., et al. (2017) Rucaparib in Relapsed, Platinum-Sensitive High-Grade Ovarian Carcinoma (ARIEL2 Part 1): An International, Multi-Centre, Open-Label, Phase 2 Trial. The Lancet Oncology, 18, 75-87. https://doi.org/10.1016/s1470-2045(16)30559-9 |
| [24] | Ledermann, J.A., Oza, A.M., Lorusso, D., Aghajanian, C., Oaknin, A., Dean, A., et al. (2020) Rucaparib for Patients with Platinum-Sensitive, Recurrent Ovarian Carcinoma (ARIEL3): Post-Progression Outcomes and Updated Safety Results from a Randomised, Placebo-Controlled, Phase 3 Trial. The Lancet Oncology, 21, 710-722. https://doi.org/10.1016/s1470-2045(20)30061-9 |
| [25] | Monk, B.J., Parkinson, C., Lim, M.C., O’Malley, D.M., Oaknin, A., Wilson, M.K., et al. (2022) A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients with Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). Journal of Clinical Oncology, 40, 3952-3964. https://doi.org/10.1200/jco.22.01003 |
| [26] | Ledermann, J., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., et al. (2012) Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer. New England Journal of Medicine, 366, 1382-1392. https://doi.org/10.1056/nejmoa1105535 |
| [27] | Pujade-Lauraine, E., Ledermann, J.A., Selle, F., Gebski, V., Penson, R.T., Oza, A.M., et al. (2017) Olaparib Tablets as Maintenance Therapy in Patients with Platinum-Sensitive, Relapsed Ovarian Cancer and a BRCA1/2 Mutation (SOLO2/ENGOT-Ov21): A Double-Blind, Randomised, Placebo-Controlled, Phase 3 Trial. The Lancet Oncology, 18, 1274-1284. https://doi.org/10.1016/s1470-2045(17)30469-2 |
| [28] | Kristeleit, R., Shapiro, G.I., Burris, H.A., Oza, A.M., LoRusso, P., Patel, M.R., et al. (2017) A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clinical Cancer Research, 23, 4095-4106. https://doi.org/10.1158/1078-0432.ccr-16-2796 |
| [29] | Watkins, J.A., Irshad, S., Grigoriadis, A. and Tutt, A.N. (2014) Genomic Scars as Biomarkers of Homologous Recombination Deficiency and Drug Response in Breast and Ovarian Cancers. Breast Cancer Research, 16, Article No. 211. https://doi.org/10.1186/bcr3670 |
| [30] | Moore, K., Colombo, N., Scambia, G., Kim, B., Oaknin, A., Friedlander, M., et al. (2018) Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine, 379, 2495-2505. https://doi.org/10.1056/nejmoa1810858 |
| [31] | Banerjee, S., Moore, K.N., Colombo, N., Scambia, G., Kim, B., Oaknin, A., et al. (2021) Maintenance Olaparib for Patients with Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation (SOLO1/GOG 3004): 5-Year Follow-Up of a Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. The Lancet Oncology, 22, 1721-1731. https://doi.org/10.1016/s1470-2045(21)00531-3 |
