Lenvatinib and pembrolizumab in endometrial cancer: patients live clearly longer

The combination of the drugs lenvatinib and pembrolizumab is approved for the treatment of women with advanced or recurrent endometrial cancer when the disease (at any stage of disease) has progressed during or after prior platinum-based therapy and curative surgical treatment or radiation is not an option. In two early benefit assessments, the German Institute for Quality and Efficiency in Health Care (IQWiG) has now examined whether the drug combination offers these patients an added benefit compared to the appropriate comparator therapy.

This examination yielded an indication of a considerable added benefit for women for whom doxorubicin or paclitaxel is the suitable therapy according to physician’s choice. However, an added benefit is not proven if another treatment option is more suitable.

For the first time in the therapeutic indication: assessment based on an RCT

In its two commissions, the Federal Joint Committee ( Gemeinsamer Bundesausschuss, G-BA) specified a therapy according to physician’s choice as appropriate comparator therapy; therefore, different treatment options could be considered as comparator therapies. In their dossiers, the two manufacturers of lenvatinib and pembrolizumab each refer to one single, identical study, KEYNOTE 775/309. With this randomized controlled trial, a meaningful study of direct comparison is available for the first time for the assessment of drugs in endometrial cancer. The combination of lenvatinib and pembrolizumab was used in its test arm, and either doxorubicin or paclitaxel was administered in its control arm.

Overall survival clearly prolonged

Most important result of the study: The median survival time of patients in the test arm was 18.3 months, in the control arm, in contrast, it was 11.4 months. In addition, there were some advantages and disadvantages of the combination therapy in other outcomes. Influenced by the clear advantage in mortality, a novelty in this therapeutic indication, IQWiG concludes: For the patients concerned, there is an indication of a considerable added benefit of the combination of lenvatinib and pembrolizumab versus doxorubicin or paclitaxel. If doxorubicin or paclitaxel are no suitable therapies, an added benefit of the new drug combination over the appropriate comparator therapy is not proven, because no study data are available for these cases.

G‑BA decides on the extent of added benefit

The dossier assessments are part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G‑BA. After their publication, the G‑BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.