Singapore-Led Studies Demonstrate Breakthrough Treatments for Challenging Women's Cancers
Key Insights
Two Singapore-led clinical trials have identified promising new treatment approaches for difficult-to-treat women's cancers, including clear cell ovarian cancer (search) and triple negative breast cancer (search).
The Lara trial showed that combining pembrolizumab and lenvatinib resulted in 40% of patients experiencing significant tumor shrinkage within 24 weeks for recurrent clear cell cancers.
A separate study found that datopotamab deruxtecan doubled progression-free survival to 10.8 months in triple negative breast cancer (search) patients compared to standard chemotherapy.
Two groundbreaking clinical trials led by Singapore researchers have demonstrated significant therapeutic advances for women facing some of the most challenging cancer diagnoses, offering new hope for patients with clear cell ovarian cancer (search) and triple negative breast cancer (search).
Combination Therapy Shows Promise for Clear Cell Cancers
The Lara trial, spearheaded by the Asia-Pacific Gynecologic Oncology Trials Group (search) under Associate Professor David Tan from the National University Cancer Institute Singapore (search) (NCIS), investigated the combination of pembrolizumab and lenvatinib for patients with recurrent clear cell endometrial and ovarian cancers resistant to standard treatments.
Clear cell cancers present unique therapeutic challenges due to their unusual cell features, abnormal blood vessel growth, and tumor microenvironment that enables immune system evasion. These cancers disproportionately affect Asian populations, comprising nearly 30% of ovarian cancers in Japan compared to approximately 12% in Western countries. In Singapore, clear cell ovarian cancers represent 30% of all new ovarian cancer cases.
The trial's mechanism of action leverages lenvatinib's ability to block tumor growth signals while making the tumor environment more accessible to immune cells, combined with pembrolizumab's enhancement of the body's immune response to recognize and attack cancer cells.
Clinical Trial Results
Conducted between 2021 and 2023 across Singapore and South Korea, the study enrolled 25 patients and achieved remarkable outcomes. Forty percent of patients experienced tumor shrinkage of 30% or more within the first 24 weeks of treatment, while 50% showed no disease progression for more than six months.
NCIS consultant Natalie Ngoi, the study's first author, emphasized the significance for rare cancer subtypes: "Trials like ours are small but mean a lot for patients with rare cancer subtypes who are often excluded from larger randomised trials that focus on the common cancer subtypes."
The findings, published in The Lancet Oncology in February, have been validated by similar results from a recent U.S. study. Professor Tan noted ongoing efforts to incorporate this combination into U.S. National Comprehensive Cancer Network guidelines, which would facilitate treatment availability in Singapore.
Antibody-Drug Conjugate Advances Triple Negative Breast Cancer Treatment
A separate international trial demonstrated significant survival improvements for patients with untreated, advanced triple negative breast cancer (search) using datopotamab deruxtecan (Dato-DXd), an antibody-drug conjugate that selectively targets and kills tumor cells while sparing healthy tissue.
Triple negative breast cancer (search) represents an aggressive subtype that disproportionately affects women under 40 and is associated with early recurrence and shorter survival. The disease accounts for approximately 15% of all breast cancer cases in Singapore, according to Professor Rebecca Dent, deputy clinical chief executive officer at the National Cancer Centre Singapore and the study's lead investigator.
Survival Outcomes
The multicountry study, published in Annals of Oncology in April, recruited 644 triple negative breast cancer (search) patients from the United States, China, Singapore, and other countries. Results showed that progression-free survival doubled to a median 10.8 months with Dato-DXd compared to chemotherapy, while overall survival also improved.
Tumor response rates demonstrated the treatment's efficacy, with 63% of patients experiencing sustained tumor shrinkage using Dato-DXd compared to 29% under standard chemotherapy.
Professor Dent highlighted a key advantage of antibody-drug conjugates: "One thing that's very consistent for all of these antibody-drug conjugates is that you can see a sustained response." This contrasts with conventional treatments where tumors may initially reduce in size but often regrow.
Regulatory Pathway and Patient Access
Both treatments are currently under regulatory review. While the pembrolizumab-lenvatinib combination is already approved in Singapore for recurrent clear cell endometrial cancer (search), it has not yet received clearance for clear cell ovarian cancers. Datopotamab deruxtecan is under review as a first-line treatment for triple negative breast cancer (search) by both the U.S. Food and Drug Administration and Singapore's Health Sciences Authority, with Professor Dent expressing optimism for approval within a year.
The research represents a significant step forward in addressing unmet medical needs for women facing these challenging cancer diagnoses, with both studies providing evidence-based treatment options for previously difficult-to-treat patient populations.