|
|
PD-1/PD-L1抑制剂治疗卵巢癌的研究进展
|
Abstract:
卵巢癌(Ovarian cancer, OC)的发病率居于女性生殖系统恶性肿瘤第三，仅次于宫颈癌和子宫内膜癌，其起病隐匿且缺乏有效的早期诊断指标，卵巢癌的预后是妇科恶性肿瘤中最差的，由于确诊时多数患者已属晚期，故化疗等综合治疗方案在卵巢癌中具有不可或缺的地位。近年来，基于对卵巢癌免疫微环境的广泛研究，提出将程序性死亡受体-1 (Programmed death 1, PD-1)/程序性死亡受体配体-1 (Programmed death ligand 1, PD-L1)抑制剂作为对卵巢癌的治疗方案。本文将对目前将PD-1/PD-L1抑制剂应用于卵巢癌的临床试验进行综述，以期为卵巢癌的综合治疗方案提供思路。
Ovarian cancer (OC) ranks third in the incidence of malignant tumours of the female reproductive system, after cervical cancer and endometrial cancer, with an insidious onset and a lack of effective early diagnostic indicators, and the prognosis of OC is the poorest among gynaecological malignant tumours. Since most patients are in the advanced stage at the time of diagnosis, chemotherapy and other comprehensive therapeutic regimens have an indispensable role in OC. In recent years, based on extensive research on the immune microenvironment of ovarian cancer, programmed death receptor-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have been proposed as a therapeutic option for ovarian cancer. In this paper, we will review the current clinical trials of PD-1/PD-L1 inhibitors applied to ovarian cancer, in order to provide ideas for comprehensive treatment options for ovarian cancer.
| [1] | Konstantinopoulos, P.A. and Matulonis, U.A. (2023) Clinical and Translational Advances in Ovarian Cancer Therapy. Nature Cancer, 4, 1239-1257. https://doi.org/10.1038/s43018-023-00617-9 |
| [2] | Dedecker, H., Teuwen, L.-A., Vandamme, T., et al. (2023) The Role of Immunotherapy in Esophageal and Gastric Cancer. Clinical Colorectal Cancer, 22, 175-182. https://doi.org/10.1016/j.clcc.2023.03.001 |
| [3] | Caruso, G., Tomao, F., Parma, G., et al. (2023) Poly(ADP-Ribose) Polymerase Inhibitors (PARPi) in Ovarian Cancer: Lessons Learned and Future Directions. International Journal of Gynecologic Cancer, 33, 431-443. https://doi.org/10.1136/ijgc-2022-004149 |
| [4] | Sánchez-Magraner, L., Gumuzio, J., Miles, J., et al. (2023) Functional Engagement of the PD-1/PD-L1 Complex but Not PD-L1 Expression Is Highly Predictive of Patient Response to Immunotherapy in Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 41, 2561-2570. https://doi.org/10.1200/JCO.22.01748 |
| [5] | Long, G., Khattak, A., et al. (2022) KEYNOTE-D36: Personalized Immunotherapy with a Neoepitope Vaccine, EVX-01 and Pembrolizumab in Advanced Melanoma. Future Oncology, 18, 3473-3480. https://doi.org/10.2217/fon-2022-0694 |
| [6] | Peng, Z., Li, M., Li, H., et al. (2023) PD-1/PD-L1 Immune Checkpoint Blockade in Ovarian Cancer: Dilemmas and Opportunities. Drug Discovery Today, 28, Article ID: 103666. https://doi.org/10.1016/j.drudis.2023.103666 |
| [7] | Liu, P., Chen, R., Zhang, X., et al. (2022) Combined PD-1/PD-L1 and Tumor-Infiltrating Immune Cells Redefined a Unique Molecular Subtype of High-Grade Serous Ovarian Carcinoma. BMC Genomics, 23, Article No. 51. https://doi.org/10.1186/s12864-021-08265-y |
| [8] | Hamanishi, J., Mandai, M., Ikeda, T., et al. (2015) Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients with Platinum-Resistant Ovarian Cancer. Journal of Clinical Oncology, 33, 4015-4022. https://doi.org/10.1200/JCO.2015.62.3397 |
| [9] | Hamanishi, J., Takeshima, N., Katsumata, N., et al. (2021) Nivolumab versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients with Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). Journal of Clinical Oncology, 39, 3671-3681. |
| [10] | Zamarin, D., Burger, R.A., Sill, M.W., et al. (2020) Randomized Phase II Trial of Nivolumab versus Nivolumab and Ipilimumab for Recurrent or Persistent Ovarian Cancer: An NRG Oncology Study. Journal of Clinical Oncology, 38, 1814-1823. https://doi.org/10.1200/JCO.19.02059 |
| [11] | Matulonis, U.A., Shapira-Frommer, R., Santin, A.D., et al. (2019) Antitumor Activity and Safety of Pembrolizumab in Patients with Advanced Recurrent Ovarian Cancer: Results from the Phase II KEYNOTE-100 Study. Annals of Oncology, 30, 1080-1087. https://doi.org/10.1093/annonc/mdz135 |
| [12] | Walsh, C.S., Kamrava, M., Rogatko, A., et al. (2021) Phase II Trial of Cisplatin, Gemcitabine and Pembrolizumab for Platinum-Resistant Ovarian Cancer. PLOS ONE, 16, E0252665. https://doi.org/10.1371/journal.pone.0252665 |
| [13] | Konstantinopoulos, P.A., Waggoner, S., Vidal, G.A., et al. (2019) Single-Arm Phases 1 and 2 Trial of Niraparib in Combination with Pembrolizumab in Patients with Recurrent Platinum-Resistant Ovarian Carcinoma. JAMA Oncology, 5, 1141-1149. https://doi.org/10.1001/jamaoncol.2019.1048 |
| [14] | Zsiros, E., Lynam, S., Attwood, K.M., et al. (2021) Efficacy and Safety of Pembrolizumab in Combination with Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Ovarian Cancer: A Phase 2 Nonrandomized Clinical Trial. JAMA Oncology, 7, 78-85. https://doi.org/10.1001/jamaoncol.2020.5945 |
| [15] | Liu, J.F., Gordon, M., Veneris, J., et al. (2019) Safety, Clinical Activity and Biomarker Assessments of Atezolizumab from a Phase I Study in Advanced/Recurrent Ovarian and Uterine Cancers. Gynecologic Oncology, 154, 314-322. https://doi.org/10.1016/j.ygyno.2019.05.021 |
| [16] | Moore, K.N., Bookman, M., Sehouli, J., et al. (2021) Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG3015/ENGOT-OV39). Journal of Clinical Oncology, 39, 1842-1855. https://doi.org/10.1200/JCO.21.00306 |
| [17] | Ak, N. and Vatansever, S. (2021) Dramatic Response to Single-Agent Atezolizumab in a Patient with MSI-H Serous Ovarian Cancer. Journal of Clinical Pharmacy and Therapeutics, 46, 1787-1791. https://doi.org/10.1111/jcpt.13364 |
| [18] | Moroney, J.W., Powderly, J., Lieu, C.H., et al. (2020) Safety and Clinical Activity of Atezolizumab plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. Clinical Cancer Research, 26, 5631-5637. https://doi.org/10.1158/1078-0432.CCR-20-0477 |
| [19] | Rocconi, R.P., Stevens, E.E., Bottsford-Miller, J.N., et al. (2022) Proof of Principle Study of Sequential Combination Atezolizumab and Vigil in Relapsed Ovarian Cancer. Cancer Gene Therapy, 29, 369-382. https://doi.org/10.1038/s41417-021-00317-5 |
| [20] | Simonelli, M., Garralda, E., Eskens, F., et al. (2022) Isatuximab plus Atezolizumab in Patients with Advanced Solid Tumors: Results from a Phase I/II, Open-Label, Multicenter Study. ESMO Open, 7, Article ID: 100562. https://doi.org/10.1016/j.esmoop.2022.100562 |
| [21] | Zamarin, D., Walderich, S., Holland, A., et al. (2020) Safety, Immunogenicity, and Clinical Efficacy of Durvalumab in Combination with Folate Receptor Alpha Vaccine TPIV200 in Patients with Advanced Ovarian Cancer: A Phase II Trial. The Journal for ImmunoTherapy of Cancer, 8, e000829. https://doi.org/10.1136/jitc-2020-000829 |
| [22] | Lampert, E.J., Zimmer, A., Padget, M., et al. (2020) Combination of PARP Inhibitor Olaparib, and PD-L1 Inhibitor Durvalumab, in Recurrent Ovarian Cancer: A Proof-Of-Concept Phase II Study. Clinical Cancer Research, 26, 4268-4279. https://doi.org/10.1158/1078-0432.CCR-20-0056 |
| [23] | Ngoi, N.Y., Heong, V., Ow, S., et al. (2020) A Multicenter Phase II Randomized Trial of Durvalumab (MEDI-4736) versus Physician’s Choice Chemotherapy in Recurrent Ovarian Clear Cell Adenocarcinoma (MOCCA). International Journal of Gynecological Cancer, 30, 1239-1242. https://doi.org/10.1136/ijgc-2020-001604 |
| [24] | Monk, B.J., Colombo, N., Oza, A.M., et al. (2021) Chemotherapy with or without Avelumab Followed by Avelumab Maintenance versus Chemotherapy Alone in Patients with Previously Untreated Epithelial Ovarian Cancer (JAVELIN Ovarian 100): An Open-Label, Randomised, Phase 3 Trial. The Lancet Oncology, 22, 1275-1289. https://doi.org/10.1016/S1470-2045(21)00342-9 |
| [25] | Pujade-Lauraine, E., Fujiwara, K., Ledermann, J.A., et al. (2021) Avelumab Alone or in Combination with Chemotherapy versus Chemotherapy Alone in Platinum-Resistant or Platinum-Refractory Ovarian Cancer (JAVELIN Ovarian 200): An Open-Label, Three-Arm, Randomised, Phase 3 Study. The Lancet Oncology, 22, 1034-1046. https://doi.org/10.1016/S1470-2045(21)00216-3 |
