In a phase II trial (LARA) reported in The Lancet Oncology, Ngoi et al found that the combination of pembrolizumab and lenvatinib was active in patients with recurrent gynecologic clear cell carcinoma.
Study Details
In the trial, 25 efficacy-eligible patients (27 in safety population) with at least one previous line of platinum-based chemotherapy and no prior immune checkpoint inhibitor exposure were enrolled at three sites in Singapore and South Korea between March 2021 and October 2023. Treatment consisted of pembrolizumab at 200 mg every 3 weeks plus lenvatinib at 20 mg daily, until progression or unacceptable toxicity or for up to 2 years. The primary outcome measure was confirmed investigator-assessed objective response rate in the first 24 weeks of treatment.
Key Findings
At data cutoff (in March 2025), median follow-up was 21.0 months (interquartile range = 12.5–25.2 months). Confirmed objective responses (all partial responses) were observed within 24 weeks in 10 of 25 patients (40%, 95% confidence interval [CI] = 21%–61%). One additional patient had an unconfirmed partial response. Stable disease was observed in another 10 patients (40%). Median duration of response was 6.6 months (95% CI = 6.0 months to not reached). Median progression-free survival was 6.4 months (95% CI = 3.4–9.5 months).
Grade 3 to 4 treatment-related adverse events occurred in 52% of 27 patients in the safety population, most commonly hypertension (22%), decreased platelet count (7%), elevated aspartate aminotransferase (7%), and elevated alanine aminotransferase (7%). Serious adverse events occurred in five patients (19%), most commonly immune-related hepatitis (7%) and decreased platelet count (7%). No treatment-related deaths were reported.
The investigators concluded: “Pembrolizumab plus lenvatinib showed promising anti-tumour activity and manageable safety in patients with recurrent [clear cell gynecologic carcinoma]…. These findings support further evaluation of this combination in randomised controlled trials.”
David S. P. Tan, MD, PhD, of the Department of Haematology-Oncology, National University Cancer Institute, Singapore, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by the National Medical Research Council (Singapore), Pangestu Family Foundation Gynaecological Cancer Research Fund, and MSD. For full disclosures of the study authors, visit thelancet.com.
