Salvage Therapy with Multikinase Inhibitors and Immunotherapy in Advanced Adrenal Cortical Carcinoma]

Kevin C. Miller, Ashish V. Chintakuntlawar, Crystal Hilger, Irina Bancos, John C. Morris, Mabel Ryder, Carin Y. Smith, Sarah M. Jenkins, Keith C. Bible

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: Median overall survival is 12 to 15 months in patients with metastatic adrenal cortical carcinoma (ACC). Etoposide, doxorubicin, and cisplatin with or without the adrenolytic agent mitotane is considered the best first-line approach in this context, but has limited activity and no curative potential; additional salvage therapeutic options are needed. Methods: Fifteen total patients with recurrent/metastatic ACC were treated with single-agent multikinase inhibitors (MKI) (n = 8), single-agent PD-1 inhibition (n = 8), or cytotoxic chemotherapy plus PD-1 inhibition (n = 4) at our institution as later-line systemic therapies in efforts to palliate disease and attempt to achieve a therapeutic response when not otherwise possible using standard approaches. Results: Two of 8 patients (25%) treated with single-agent MKI achieved a partial response (PR), including 1 PR lasting 23.5 months. Another 3 patients (38%) had stable disease (SD); median progression-free survival (PFS) with single-agent MKI was 6.4 months (95% confidence interval [CI] 0.8-not reached). On the other hand, 2 of 12 patients (17%) treated with PD-1 inhibitors (either alone or in combination with cytotoxic chemotherapy) attained SD or better, with 1 patient (8%) achieving a PR; median PFS was 1.4 months (95% CI 0.6-2.7). Conclusions: Our single-institution experience suggests that select ACC patients respond to lateline MKI or checkpoint inhibition despite resistance to cytotoxic agents. These treatments may be attractive to ACC patients with limited other therapeutic options. The use of MKI and immunotherapy in ACC warrants prospective investigation emphasizing parallel correlative studies to identify biomarkers that predict for response. c Endocrine Society 2020. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (, which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalJournal of the Endocrine Society
Issue number7
StatePublished - 2020


  • Adrenal cancer
  • Adrenal cortical carcinoma
  • Adrenocortical carcinoma
  • Checkpoint inhibition
  • Immunotherapy
  • Tyrosine kinase inhibition

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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