Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma

Abstract

BackgroundThere is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.MethodsA retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC.ResultsEight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21–49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2–9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8–not reached) and median duration of therapy was 8.5 months (range 2–22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events.ConclusionsIn our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.

Survival Predictors of Metastatic Adrenocortical Carcinoma: a SEER-based Retrospective Study

“…There were more patients with N0 (67.8%) than patients with N1(22.3%). [4,15,16]. There were quantitative differences from previous reports that the incidence of bone metastases was higher in our study [4,13].…”

Synergistic Effects of Lenvatinib (E7080) and MEK Inhibitors against Anaplastic Thyroid Cancer in Preclinical Models

“…A recent study has revealed the importance of combination therapy for lenvatinib. Lenvatinib plus immunotherapy has been used for advanced solid tumors, such as adrenal cortical carcinoma, non-small-cell lung cancer, hepatocellular carcinoma, and head and neck squamous cell carcinoma [ 25 , 26 , 27 , 28 ]. Antiangiogenic therapy is known to reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy [ 29 , 30 ].…”

Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance

“…The preclinical rational for a synergistic activity between ICI and mitotane is required, as it has been suggested by tumor responses achieved in different clinical studies. Lenvatinib is another partner for pembrolizumab combination in a retrospective series with heavily pretreated metastatic ACC patients [ 89 ]. The potential immunomodulation induced by lenvatinib has been suggested as a potential mechanism of synergy between this drug and ICI.…”