7959 Combination Therapy Of Multi-Targeted Tyrosine Kinase Inhibitors And Immune Checkpoint Inhibitors In Advanced Adrenocortical Carcinoma

Abstract Disclosure: F. Yaylaci Mert: None. V. Balderrama Brondani: None. L.P. Marcal: None. M. Campbell: None. C. Jimenez: None. J. Varghese: None. A. Shah: None. M.A. Habra: None. Background: Adrenocortical carcinoma (ACC) is a rare cancer with limited response to systemic chemotherapies. Monotherapy with multi-targeted tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) in ACC patients has limited efficacy. Combining TKIs with ICIs increased response rates in other malignancies but the efficacy of this approach in ACC is still unknown. This retrospective study aims to evaluate the efficacy and safety of the combined use of TKIs and ICIs in patients with advanced ACC. Methods: A single-center, retrospective cohort study in patients with advanced ACC treated with the combination of TKIs and ICIs. Response rates, progression-free survival (PFS), overall survival (OS) calculated from the time of combination, disease control rate (DCR), and safety profile were the main study objectives. Results: Seventeen patients were treated with combination therapy of TKI (lenvatinib or cabozantinib) and ICI (pembrolizumab) between January 2017 and December 2023. Eleven patients were women, the median age was 43.4 years (range 21.9-66.6), and 8 (47.1%) patients presented cortisol-producing tumors. All patients had prior systemic therapy, median of 3 (range 1-9) lines of therapy. The median duration of TKI+ICI therapy was 7.1 months (range 0.7-69.7). The treatment was discontinued in one patient due to a grade 3 adverse event (gastrointestinal fistula) after 1.6 months of treatment. Best overall responses were as follows: partial response 2 (13%), stable disease 8 (53%), and progressive disease 5 (34%). DCR was 58.8%. Median PFS was 7.1 months (range 0.7-66.4). One death occurred during the study due to disease progression. The median OS was 21.3 months (range 3.3-70.3). At the time of this report, 7 patients (41%) were still alive. Conclusion: The combined use of TKIs and ICIs in heavily treated ACC patients is associated with occasional durable responses and has a predictable and manageable side effect profile. This combination is worthy of a prospective clinical trial to validate the findings and establish new lines of therapy for this rare disease. Presentation: 6/2/2024