Lenvatinib and Pembrolizumab Combination Therapy for the Treatment of Endometrial Cancer: A Real-World Study

The combination therapy of lenvatinib and pembrolizumab (lenva + pembro) is a newer treatment option for patients with recurrent or advanced endometrial cancer (aEC). This therapy was fully approved by the US Food and Drug Administration on July 21, 2021, and subsequently added to the National Comprehensive Cancer Network (NCCN) guidelines for treatment of patients with mismatch repair proficient/nonmicrosatellite instability-high aEC for second-line treatment in 2022. Due to the recency of the treatment approval, there is limited real-world evidence on its use and dosing patterns. As such, Keiko Wada, MS, IQVIA Inc, and colleagues sought to analyze the treatment and dosing patterns of this combination therapy for patients with EC in the US (Future Oncol. 2023 Oct 13. doi:10.2217/fon-2023-0058. Online ahead of print).

The researchers pulled data on oral medication prescriptions for lenvatinib and infusions of pembrolizumab from IQVIA’s longitudinal prescription claims database, which is also linked to the medical claims database. They used this data to examine the treatment patterns of the lenva + pembro therapy, which included the number of lenvatinib claims, the number of pembrolizumab administrations, duration of lenva + pembro therapy, and the reason for ending the therapy. They also reviewed dosing patterns of the combination therapy, which consisted of the starting dose and/or dosing interval and change in dose and/or dosing interval, during ≥1 month follow-up.

The study included 245 female patients with EC (aged 18 years or older) who initiated lenva + pembro therapy as second-line (2L) or third-line or later (≥3L) treatment between September 17, 2019, and June 30, 2021. The researchers defined the start date of the combination therapy (index date) as the first lenvatinib claim date or the first pembrolizumab claim date, whichever was first. If patients previously had other primary cancers, ≥1 prior lenvatinib or pembrolizumab claims before the index date, ≥1 pembrolizumab or lenvatinib claims outside of the selection window, or if they were participating in a clinical trial during the study period, they were not included in the study.

Wada and colleagues stratified the patients into two mutually exclusive cohorts: (1) Patients who received lenva +pembro as 2L treatment (2L cohort: 110 patients with a median age of 67 years old) and (2) patients who received the combination therapy as 3L or later treatment (≥3L cohort: 135 patients with a median age of 66 years old). If they had initiated treatment within 30 days, it was considered as part of the same line of therapy (LOT). If patients had no prior observed LOT, they were not included in the study.

The researchers found that 70.9% of the 2L cohort and 63.7% of the ≥3L cohort began the lenva + pembro treatment at the label-recommended 20 mg daily starting dose, while less than 40% of total patients changed the dosing of lenvatinib. In addition, more than 87% of the patients followed the label-recommended dose and interval for pembrolizumab. Over the median follow-up period since the start of treatment (7.3 months for 2L patients and 8.7 months for ≥3L patients), the median (95% CI) time span of therapy was 5.1 (4.7-6.1) months for 2L patients and 5.8 (4.2-7.3) months for ≥3L patients. Although 35.6% of patients discontinued the combination therapy, most stuck to the treatment at data cut-off.

Additional findings included that both cohorts had a low burden of comorbidities at baseline (mean Charlson Comorbidity Index score of 0.8, excluding cancer). Hypertension and diabetes were the most reported comorbidities among both cohorts. Many participants also reported that they had surgery for EC prior to starting the combination therapy (31.8% of the 2L patients and 28.9% of the ≥3L patients), with total hysterectomy being the most common for 18.2% of the 2L patients and 17.8% for the ≥3L patients. In addition, most patients in both cohorts (≥93.6%) were treated with chemotherapy before they started lenva + pembro therapy.

The researchers acknowledge that their study had several limitations, including having a small sample size and limited follow-up time (30 days) due to the recency of the combination therapy approval and general limited availability of claims data. They also note administrative barriers, such as the potential misclassification of diagnoses and lack of available biomarker information to determine patients’ microsatellite instability or mismatch repair status. In addition, as all participants in the study were US based, the study’s findings may not be applicable to other international populations.

“Our retrospective cohort study using a nationally representative claims database is one of the first studies that provide early evidence on real-world utilization and dosing patterns of lenvatinib and pembrolizumab combination therapy among patients diagnosed with EC in clinical practice in USA, when used in the 2L or later settings,” wrote the authors.

Overall, the study found that the patients in both cohorts initiated the recommended doses of 20 mg daily for lenvatinib and then continued the label-recommend dose (20 mg) when starting the lenva + pembro therapy. To build further on this study, the authors recommend including more clinical data, information on the patients’ disease stages, and clinical outcomes. Also, as the study’s follow-up time was limited, they note that future studies should have longer follow-up times and larger sample sizes.