Low doses of the immunotherapy medication pembrolizumab could be effective in Asian patients with endometrial cancer (EC), who tend to have a lower body mass index (BMI) than Western populations, according to a recently published study in the Journal of the Formosan Medical Association.
Immunotherapy has significantly improved outcomes in advanced EC, particularly when combined with chemotherapy. However, most clinical trials have focused on Western populations, leaving important questions about efficacy and dosing in Asian patients.
A recent single-center study addressed this gap, suggesting that a lower dose of pembrolizumab (100 mg) may be as effective as the standard 200 mg dose when used in combination therapy.
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In a newly published letter, the study’s authors responded to peer commentary highlighting the importance of molecular profiling and regional considerations in precision oncology. They agreed that the observed dose equivalence between 100 mg and 200 mg pembrolizumab requires deeper investigation, especially since Asian populations tend to have a lower BMI than Western cohorts. This physiological difference could affect drug metabolism and efficacy.
Importantly, validating a lower fixed dose could have major pharmacoeconomic benefits. Reduced dosing may improve accessibility to immunotherapy in healthcare systems with limited financial resources, a critical step toward equitable cancer care.
The authors also emphasized the need to incorporate molecular classification, such as POLE mutations, mismatch repair deficiency (dMMR), p53 status and NSMP subtype profiling to guide treatment decisions. They noted that advanced tools like multiplex immunohistochemistry and single-cell RNA sequencing will be essential to better understand heterogeneous responses, particularly in patients with dMMR or p53-abnormal tumors.
Another key point raised was the underrepresentation of Asian patients in major immunotherapy trials. For example, the DUO-E trial, which had the highest Asian enrollment to date, showed a relatively less favorable response to immunotherapy in this subgroup.
The authors propose that differences in genetics, lifestyle, diet or environmental exposures may contribute to these disparities. They advocate for more regionally tailored clinical trials to ensure personalized treatment approaches are truly inclusive.
“Finally, we echo the call for prospective, multicenter randomized trials specifically designed for Asian populations. Such trials should not only validate optimal dosing strategies but also incorporate comprehensive biomarker analyses to refine patient selection and manage ethnicity-specific toxicities,” the authors concluded.
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