Single and Combination of Therapy Pembrolizumab in Platinum-Resistant Ovarian Cancer: A Systematic Review of Randomized Controlled Trials
A systematic review of randomized controlled trials
Abstract
Platinum-resistant ovarian cancer (PROC) remains one of the most challenging gynecologic malignancies, with limited therapeutic options and poor clinical outcomes. The emergence of immune checkpoint inhibitors, particularly pembrolizumab, has introduced new therapeutic possibilities; however, its clinical efficacy in PROC remains inconsistent and incompletely understood. This systematic review aims to evaluate the efficacy and clinical outcomes of pembrolizumab administered as single-agent and combination therapy in patients with platinum-resistant ovarian cancer, with particular emphasis on survival endpoints and biomarker-based patient stratification. A systematic search of major electronic databases was conducted to identify randomized controlled trials assessing pembrolizumab in PROC. Eligible studies were screened based on predefined inclusion and exclusion criteria. Data extraction focused on objective response rate (ORR), progression-free survival (PFS), overall survival (OS), safety profiles, and molecular or immunological biomarkers. Pembrolizumab monotherapy demonstrated limited antitumor activity, characterized by low ORR and modest survival benefits restricted to selected patient subgroups. In contrast, combination therapies incorporating pembrolizumab with chemotherapy, anti-angiogenic agents, or epigenetic modulators consistently showed improved ORR and prolonged PFS. Pembrolizumab exhibits greater clinical potential in platinum-resistant ovarian cancer when used in combination regimens and guided by comprehensive biomarker stratification. Future trials should prioritize optimized combination strategies and multidimensional biomarker approaches to enhance patient selection and therapeutic efficacy.
Downloads
References
Chen, S., Xie, P., Cowan, M., Huang, H., Cardenas, H., Keathley, R., Tanner, E. J., Fleming, G. F., Moroney, J. W., & Pant, A. (2022). Epigenetic priming enhances antitumor immunity in platinum-resistant ovarian cancer. The Journal of Clinical Investigation, 132(14).
Fasya, A. G. (2016). Potensi antikanker dan antioksidan serta identifikasi isolat steroid mikroalga Chlorella sp. https://repository.uin-malang.ac.id/2625/
Fukumura, D., Kloepper, J., Amoozgar, Z., Duda, D. G., & Jain, R. K. (2018). Enhancing cancer immunotherapy using antiangiogenics: Opportunities and challenges. Nature Reviews Clinical Oncology, 15(5), 325–340.
Hamanishi, J., Mandai, M., Iwasaki, M., Okazaki, T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K., & Minato, N. (2007). Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proceedings of the National Academy of Sciences, 104(9), 3360–3365.
Harari, A., Graciotti, M., Bassani-Sternberg, M., & Kandalaft, L. E. (2020). Antitumour dendritic cell vaccination in a priming and boosting approach. Nature Reviews Drug Discovery, 19(9), 635–652.
Hendrikse, C. S. E., Theelen, P. M. M., Van Der Ploeg, P., Westgeest, H. M., Boere, I. A., Thijs, A. M. J., Ottevanger, P. B., Van De Stolpe, A., Lambrechts, S., & Bekkers, R. L. M. (2023). The potential of RAS/RAF/MEK/ERK (MAPK) signaling pathway inhibitors in ovarian cancer: A systematic review and meta-analysis. Gynecologic Oncology, 171, 83–94.
Lheureux, S., Gourley, C., Vergote, I., & Oza, A. M. (2019). Epithelial ovarian cancer. The Lancet, 393(10177), 1240–1253.
Listiyana, A., Astari, L. F., & Indradmojo, C. (2024). Uji Toksisitas Chrysanthemum cinerariifolium dan Potensinya terhadap Penurunan Proliferasi Sel pada Kejadian Kanker Lidah. https://repository.uin-malang.ac.id/21901/
Matulonis, U. A., Shapira-Frommer, R., Santin, A. D., Lisyanskaya, A. S., Pignata, S., Vergote, I., Raspagliesi, F., Sonke, G. S., Birrer, M., & Provencher, D. M. (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(7), 1080–1087.
Mutiah, R. (2021). Peran fitofarmaka dalam pencegahan dan terapi kanker: Peluang, tantangan dan strategi. https://repository.uin-malang.ac.id/7876/
Odunsi, K. (2017). Immunotherapy in ovarian cancer. Annals of Oncology, 28, viii1–viii7.
Sigalotti, L. D. G., Klapp, J., Rendón, O., Vargas, C. A., & Peña-Polo, F. (2016). On the kernel and particle consistency in smoothed particle hydrodynamics. Applied Numerical Mathematics, 108, 242–255.
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., & Atkins, M. B. (2012). Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. New England Journal of Medicine, 366(26), 2443–2454.
Walsh, C. S., Kamrava, M., Rogatko, A., Kim, S., Li, A., Cass, I., Karlan, B., & Rimel, B. J. (2021). Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. PLoS One, 16(6), e0252665.
Zsiros, E., Lynam, S., Attwood, K. M., Wang, C., Chilakapati, S., Gomez, E. C., Liu, S., Akers, S., Lele, S., & Frederick, P. J. (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(1), 78–85.
Copyright (c) 2026 Muhamad Ibnu Malkan

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work’s authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal’s published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.



