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Key unmet needs across the advanced or recurrent endometrial cancer (EC) treatment landscape highlight opportunities to power scientific progress for patients who have limited options.1-3

Patients face poor long-term outcomes and limited options

EC is rising in incidence and mortality, and Black women are often diagnosed at a higher grade and stage of EC compared to white women. For patients with advanced or recurrent EC, treatment options are limited, and approximately half of patients discontinue treatment following each line of therapy from 1L to 3L. Further investigation into tumor biology, resistance mechanisms, and disease progression may help inform new approaches to extend survival and improve outcomes.1,4-7

Flip each card to see how key unmet needs impact patients

About

33%

OF PATIENTS

are diagnosed with advanced regional or metastatic disease7,8

Comorbidities and social determinants of health contribute to a heightened risk of advanced or recurrent EC in underserved populations.6,7,9

Nearly

50%

OF PATIENTS

stop treatment
after 2L5

Discontinuation after 2L may reflect a need for better long-term outcomes and better efficacy from treatments.5

Approximately

20%

OF PATIENTS

with distant metastases survive beyond 5 years5

Metastatic disease is associated with greater molecular heterogeneity, which can contribute to resistance and poor treatment response.5,7,10,11

Survival decreases with each line of therapy (LOT) in advanced or recurrent EC5

Treatment patterns in advanced or recurrent endometrial cancer. Adapted from Coleman RL, Garside J, Hurteau J, Nguyen J, Kobayashi M. Treatment patterns and outcomes among patients with advanced or recurrent endometrial cancer initiating first-line therapy in the United States. J Health Econ Outcomes Res. 2023;10(2):82-90. Licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/).

Overall survival was evaluated in a real-world study of 1961 patients with advanced or
recurrent EC who initiated at least 1 line of therapy.5

With limited treatment options in 2L+, uncovering alternative molecular pathways may offer hope for advancing outcomes in advanced or recurrent EC.1,2,5
With limited treatment options in 2L+, uncovering alternative molecular pathways may offer hope for advancing outcomes in advanced or recurrent EC. 1,2,5

Exploring key cell-surface targets shaping the future of EC treatments

Research continues to uncover the molecular factors that drive disease progression and resistance in advanced or recurrent EC. Certain cell-surface proteins expressed on tumor cells, including those involved in signaling, cell survival, and immune evasion, are under investigation for their role in the advanced or recurrent setting.6,12,13

Understanding the expression and function of these proteins may offer insights into the complex behavior of advanced or recurrent EC as well as support ongoing scientific efforts.

Immune cell with Trop-2 protein. Immune cell with HER2 protein. Immune cell with FRa protein. Immune cell with B7-H4 protein.

A cell-surface protein highly expressed across EC subtypes, regardless of histology or molecular classification.

  • Trop-2 is linked to tumor cell growth, proliferation, invasion, metastasis, and survival through multiple pathways
  • The consistent expression of Trop-2 has positioned it as a focus of ongoing clinical development
Immune cell with Trop-2 protein.

A transmembrane tyrosine kinase receptor that contributes to cell growth and survival through the MAPK and PI3K/AKT pathways.

  • Treatment with HER2-directed therapies requires HER2 IHC testing
  • In one study, HER2 overexpression was observed in approximately 60% of endometrial cancers (IHC 1+/2+/3+)
Immune cell with HER2 protein.

A cell-membrane protein often overexpressed in serous and epithelial endometrial tumors.

  • It facilitates folate transport into cells, contributing to tumor growth and proliferation
  • Endometrial tumors often show elevated levels of folate receptor alpha (FRa), with approximately 64% testing positive for FRa expression
Immune cell with FRa protein.

A transmembrane protein that binds to a receptor on immune cells, allowing tumors to evade immune detection.

  • B7-H4 is expressed in approximately 72% of endometrial cancers
Immune cell with B7-H4 protein.
circuit-container As research advances, opportunities are emerging that may address a broader range of patients.1,10,22
circuit-container As research advances, opportunities are emerging that may address a broader range of patients.1,10,22

Driving research where options are few

Ongoing research continues to clarify the biological diversity of EC, including its molecular heterogeneity, immune-related pathways, and resistance mechanisms that limit current approaches. Treatments that act broadly and reflect the diversity of real-world populations may help to address this complexity.22-24

Building on a legacy of innovation in oncology, Gilead is committed to expanding research and improving outcomes in cancer types marked by high unmet need and persistent disparities. This work drives solutions for patients, particularly women of color, who have been historically underrepresented in cancer research.

1L=first line; 2L=second line; 3L=third line; AKT=protein kinase B; B7-H4=B7 homologue 4; EC=endometrial cancer; FRa=folate receptor alpha; HER2=human epidermal growth receptor 2; IHC=immunohistochemistry; IQR=interquartile range; LOT=line of therapy; MAPK=mitogen-activated protein kinase; PFS=progression-free survival; PI3K=phosphatidylinositol 3-kinase; Trop-2=trophoblast cell-surface antigen-2.

References

  1. Tillmanns T, Masri A, Stewart C, et al. Advanced endometrial cancer–the next generation of treatment: a Society of Gynecologic Oncology Journal Club clinical commentary. Gynecol Oncol Rep. 2024;55:101462. doi:10.1016/j.gore.2024.101462
  2. Scott B, Lorusso D. Advancements in endometrial cancer research in 2024. EMJ Oncol. 2025;13[Suppl1]:2-3. doi:10.33590/emjoncol/NINN2044
  3. Salmon A, Lebeau A, Streel S, et al. Locally advanced and metastatic endometrial cancer: current and emerging therapies. Cancer Treat Rev. 2024;129:102790. doi:10.1016/j.ctrv.2024.102790
  4. Vetter M, Powell MA. Evolving treatment landscape in endometrial cancer. healthbook TIMES Onco Hema. 2024;20(2):40-47. doi:10.36000/HBT.OH.2024.20.149
  5. Coleman RL, Garside J, Hurteau J, Nguyen J, Kobayashi M. Treatment patterns and outcomes among patients with advanced or recurrent endometrial cancer initiating first-line therapy in the United States. J Health Econ Outcomes Res. 2023;10(2):82-90. doi:10.36469/001c.87853
  6. Huang D, Li S, Bai Y, Wang Y. Efficacy and safety of immune checkpoint inhibitors for advanced or recurrent endometrial cancer: a systematic review and network meta-analysis. BMC Cancer. 2024;24(1):1298. doi:10.1186/s12885-024-13058-z
  7. Makker V, MacKay H, Ray-Coquard I, et al. Endometrial cancer. Nat Rev Dis Primers. 2021;7(1):88. doi:10.1038/s41572-021-00324‐8
  8. Buras AL, Mallen A, Wenham R, Montejo M. Stage IIIC endometrial cancer review: current controversies in adjuvant therapy. Gynecol Oncol Rep. 2021;36:100754. doi:10.1016/j.gore.2021.100754
  9. Fucinari J, Elshaikh MA, Ruterbusch JJ, et al. The impact of race, comorbid conditions, and obesity on survival endpoints in women with high grade endometrial carcinoma. Gynecol Oncol. 2021;162(1):134-141. doi:10.1016/j.ygyno.2021.04.036
  10. Sinai Borker N, Sajimon J, Subhadarshini S, et al. Role of intratumoral heterogeneity in metastatic progression and drug resistance. Discov Oncol. 2025;16(1):1689. doi:10.1007/s12672-025-03322-4
  11. Molefi T, Mabona L, Hull R, Sebitloane M, Dlamini Z. From genes to clinical practice: exploring the genomic underpinnings of endometrial cancer. Cancers. 2025;17(2):320. doi:10.3390/cancers17020320
  12. Shi X, Tang K, Zhang Q, et al. Antibody-drug conjugate combinations in cancer treatment: clinical efficacy and clinical study perspectives. Front Pharmacol. 2025;16:1556245. doi:10.3389/fphar.2025.1556245
  13. Fasih S, Welch S, Lohmann AE. Antibody-drug conjugates: a start of a new era in gynecological cancers. Curr Oncol. 2024;31(11):7088-7106. doi:10.3390/curroncol31110522
  14. Goldenberg DM, Stein R, Sharkey RM. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget. 2018;9(48):28989-29006. doi:10.18632/oncotarget.25615
  15. Tong Y, Fan X, Liu H, Liang T. Advances in Trop-2 targeted antibody-drug conjugates for breast cancer: mechanisms, clinical applications, and future directions. Front Immunol. 2024;15:1495675. doi:10.3389/fimmu.2024.1495675
  16. Soberanis Pina P, Lheureux S. Novel molecular targets in endometrial cancer: mechanisms and perspectives for therapy. Biologics Targets Ther. 2024;18:79-93. doi:10.2147/BTT.S369783
  17. Hacker KE, Fleming KA, Gupta M, Pothuri B. HER2 expression in an endometrial cancer cohort. Gynecol Oncol. 2025;201:1-6. doi:10.1016/j.ygyno.2025.07.024
  18. Zhang J, Li Y, Wang L, Zhang Y, Zhang Q, Liu J. Folate receptor alpha promotes endometrial carcinoma cell proliferation and inhibits apoptosis by regulating the ERK signaling pathway. Int J Clin Exp Med. 2019;12(7):8791-8798.
  19. Phipps M, Falchook GS. B7 Homolog 4 (B7-H4)-directed agents in oncology clinical trials: a review. J Immunother Precis Oncol. 2025;8(2):153-160. doi:10.36401/JIPO-24-34
  20. Wang JY, Wang WP. B7-H4, a promising target for immunotherapy. Cell Immunol. 2020;347:104008. doi:10.1016/j.cellimm.2019.104008
  21. Zong L, Yu S, Mo S, et al. B7-H4 further stratifies patients with endometrial cancer exhibiting a nonspecific molecular profile. Arch Pathol Lab Med. 2023;147(11):1288-1297. doi:10.5858/arpa.2022-0182-OA
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