Although lowering the starting dose of lenvatinib for patients with advanced and recurrent endometrial cancer (EC) reduces toxicity, it may also lessen the effectiveness of the drug, according to findings published in Frontiers in Oncology.
The study evaluated the combination of lenvatinib and pembrolizumab, a drug regimen that was supported by the KEYNOTE-775 clinical trial. The trial found that together, these drugs improved overall survival and progression-free survival compared to chemotherapy.
“However, the recommended 20 mg daily lenvatinib dose often results in significant toxicity, limiting its use in clinical practice,” the authors cautioned. Side effects may include weight loss, shortness of breath, fatigue and musculoskeletal disorders.
The study included 92 patients with EC, 14.1% of whom received 20 mg daily. Of those receiving 20 mg, 54% had to lower their dose due to side effects.
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Results showed that 74% of participants experienced either moderate or severe adverse events. Additionally, while 46% of patients taking less than 10 mg further decreased their dose, 37% of patients taking 10 or more mg decreased their dose. Intolerable fatigue was one of the most frequent causes of dose reduction.
The authors found that about half of patients in each group interrupted treatment. Infections were a more common cause for interruption in the higher-dose group.
The most commonly reported reasons for permanent discontinuation were clotting events (deep vein thrombosis and pulmonary embolism), diarrhea and hypertension.
Notably, the one-year overall survival and progression-free survival did not differ between the low- and high- dose groups. However, once the authors developed a statistical model that adjusted for age, individuals in the reduced-dose group were more likely to experience progression or death compared to the higher-dose group.
The researchers advise that future studied be conducted to determine an optimal dose of lenvatinib for patients with EC, considering both safety and efficacy.
“Clinicians should carefully weigh the risks and benefits of various lenvatinib starting doses,” the authors concluded. “Our findings suggest that intermediate starting doses may provide a more favorable balance between efficacy and tolerability.”
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