Combination therapy of multi-targeted tyrosine kinase inhibitors and immune checkpoint inhibitors for advanced adrenocortical carcinoma

Feyza Yaylaci; Vania Balderrama-Brondani; Leonardo P. Marcal; Camilo Jimenez; Jeena Varghese; Amishi Y. Shah; Roland Bassett; Habra Mouhammed Amir; Matthew T. Campbell

doi:10.1530/endoabs.107.007

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Endocrine Abstracts (2024) 107 007 | DOI: 10.1530/endoabs.107.007

IACS9 9th International Adrenal Cancer Symposium 2024 Abstracts (18 abstracts)

Combination therapy of multi-targeted tyrosine kinase inhibitors and immune checkpoint inhibitors for advanced adrenocortical carcinoma

Feyza Yaylaci ¹ , Vania Balderrama-Brondani ¹ , Leonardo P. Marcal ² , Camilo Jimenez ¹ , Jeena Varghese ¹ , Amishi Y. Shah ³ , Roland Bassett ⁴ , Mouhammed Amir Habra ^1* & Matthew T. Campbell ^3*

Author affiliations

^*Equally contributed as joint senior authors
¹Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ²Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ³Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA ⁴Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Background: Adrenocortical carcinoma (ACC) is a rare malignancy with limited treatment options. There is limited data about the combined use of multi-targeted tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) in ACC.

Methods: A retrospective study describing the activity and safety of the combination treatment of lenvatinib/pembrolizumab (LEN/PEM) and cabozantinib/pembrolizumab (CABO/PEM) in advanced ACC patients treated in a single institution.

Results: Twenty-four patients (13 females, 54.1%) received either LEN/PEM (17 patients, 70.9%) or CABO/PEM (7 patients, 29.1%) with a median age of 42.5 years (21.2-64.8 years) at the time of starting therapy. All patients failed prior therapy with median lines of prior treatment of 3 (range 1-8). Six patients (25%) had cortisol overproduction at the start of the combination therapy. The median follow-up time was 12.52 months (range, 0.62-72.87) and the median duration of the combination therapy was 5.4 months (range, 0.6-69.6 months). Median progression-free survival (PFS) and overall survival were 8.05 months (4.83-17.48, 95% CI) and 17.48 months (9.89-NA, 95% CI) respectively. The best responses included 3 (12.5%) partial response (PR), 11 (45.8%) stable disease (SD), and 9 (37.5%) progressive disease (PD). There was 1 non-evaluable patient for response. The disease control rate (DCR) was 58.3% and the overall response rate (ORR) was 13%. In two patients, the treatment was discontinued due to grade 3 ICI-induced pneumonitis and autoimmune hepatitis.

Conclusions: In the absence of established salvage therapy in ACC, the combination of multi-targeted TKI/ICI has been associated with clinical benefit in almost half of the subjects. Factors associated with response are worthy of further investigation to properly select patients for future trials testing the combined use of ICIs and TKIs in ACC.