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Horm Metab Res 2021; 53(05): 285-292
DOI: 10.1055/a-1453-0806
Review

Advanced Adrenocortical Carcinoma: Current Perspectives on Medical Treatment

Alexandra Novais Araújo
1   Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
,
Maria João Bugalho
1   Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
2   Faculty of Medicine, Lisbon University, Lisbon, Portugal
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Abstract

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. For stage I and II tumors, surgery is a curative option, but even in these cases recurrence is frequent. Practical guidelines advocate a combination of mitotane with etoposide, doxorubicin, and cisplatin as first-line therapy for metastatic adrenocortical carcinoma. However, this scheme presents limited efficacy and high toxicity. The use of Immune Checkpoint Inhibitors (ICI) and multi-Tyrosine Kinase Inhibitors (mTKI) has modified the approach of multiple malignancies. The expectation of their applicability on advanced adrenocortical carcinoma is high but the role of these new therapies persists unclear. This article provides a short summary of last years’ findings targeting outcomes, limitations, and adverse effects of these new therapeutic approaches. The results of recent trials and case series pointed pembrolizumab as the most promising drug among these new therapies. It is the most often used ICI and the one presenting the best results with less related adverse effects when in comparison to the standard treatment with mitotane. Hereafter, the identification of specific molecular biomarkers or immune profiles associated with ICI or mTKI good response will facilitate the selection of candidates for these therapies. So far, microsatellite instability and Lynch Syndrome related germline mutations are suggested as predictive biomarkers of good response. Contrarywise, cortisol secretion has been associated with more aggressive ACC tumors and potentially poor responses to immunotherapy.

Key words

immune checkpoint inhibitors - multi-tyrosine kinase inhibitors - immunotherapy - mitotane


Publikationsverlauf

Eingereicht: 29. Dezember 2020

Angenommen nach Revision: 11. März 2021

Artikel online veröffentlicht:
07. Mai 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Custódio G, Komechen H, Figueiredo FRO. et al. Molecular epidemiology of adrenocortical tumors in southern Brazil. Mol Cell Endocrinol 2012; 351: 44-51
    CrossrefPubMedGoogle Scholar
  • 2 Altieri B, Ronchi CL, Kroiss M. et al. Next-generation therapies for adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab 2020; 34: 101434
    CrossrefPubMedGoogle Scholar
  • 3 Fassnacht M, Dekkers OM, Else T. et al. European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 2018; 179: G1-G46
    CrossrefPubMedGoogle Scholar
  • 4 Else T, Kim AC, Sabolch A. et al. Adrenocortical carcinoma. Endocr Rev 2014; 35: 282-326
    CrossrefPubMedGoogle Scholar
  • 5 Fiorentini C, Grisanti S, Cosentini D. et al. Molecular drivers of potential immunotherapy failure in adrenocortical carcinoma. J Oncol 2019; 2019: 1-7
    CrossrefPubMedGoogle Scholar
  • 6 Chortis V, Bancos I, Nijman T. et al. Urine steroid metabolomics as a novel tool for detection of recurrent adrenocortical carcinoma. J Clin Endocrinol Metab 2020; 105: e307-e318
    CrossrefPubMedGoogle Scholar
  • 7 Brabo EP, Moraes AB, Neto LV. The role of immune checkpoint inhibitor therapy in advanced adrenocortical carcinoma revisited: Review of literature. J Endocrinol Invest 2020; 43: 1531-1542
    CrossrefPubMedGoogle Scholar
  • 8 Pommier RF, Brennan MF. An eleven-year experience with adrenocortical carcinoma. Surgery 1992; 112: 96370. discussion 70–71
    PubMedGoogle Scholar
  • 9 Stojadinovic A, Ghossein RA, Hoos A. et al. Adrenocortical carcinoma: Clinical, morphologic, and molecular characterization. J Clin Oncol 2002; 20: 941-950
    CrossrefPubMedGoogle Scholar
  • 10 Kong J, Zheng J, Cai J. et al. A nomogram for individualized estimation of survival among adult patients with adrenocortical carcinoma after surgery: a retrospective analysis and multicenter validation study. Cancer Commun 2019; 39: 80
    CrossrefPubMedGoogle Scholar
  • 11 Tella SH, Kommalapati A, Yaturu S. et al. Predictors of survival in adrenocortical carcinoma: An analysis from the National Cancer Database. J Clin Endocrinol Metab 2018; 103: 3566-3573
    CrossrefPubMedGoogle Scholar
  • 12 Bedrose S, Daher M, Altameemi L. et al. Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions. Cancers (Basel) 2020; 12: 508
    CrossrefPubMedGoogle Scholar
  • 13 Bergenstal D, Lipsett MB, Moy R. et al. Regression of Adrenal Cancer and Suppression of Adrenal Function in Man by o,p′-DDD11. Biological Activities of Steroids in Relation to Cancer. Pincus G, Vollmer EP. Maryland: Academic Press,. 1960. 463-475
    PubMedGoogle Scholar
  • 14 Terzolo M, Angeli A, Fassnacht M. et al. Adjuvant Mitotane Treatment for Adrenocortical Carcinoma. N Engl J Med 2007; 356: 2372-2380
    CrossrefPubMedGoogle Scholar
  • 15 Kulk M, Shah M, Benson A. et al. NCCN Clinical Practice Guidelines in Oncology:Neuroendocrine tumors. J Natl Compr Canc Netw 2015; 13 (01) 78-108
    CrossrefPubMedGoogle Scholar
  • 16 Fassnacht M, Terzolo M, Allolio B. et al. Combination Chemotherapy in Advanced Adrenocortical Carcinoma. N Engl J Med 2012; 366: 89-97
    CrossrefPubMedGoogle Scholar
  • 17 Sperone P, Ferrero A, Daffara F. et al. Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study. Endocr Relat Cancer 2010; 17: 445-453
    CrossrefPubMedGoogle Scholar
  • 18 Barlaskar FM, Spalding AC, Heaton JH. et al. Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma. J Clin Endocrinol Metab 2009; 94: 204-212
    CrossrefPubMedGoogle Scholar
  • 19 Fassnacht M, Berruti A, Baudin E. et al. Linsitinib (OSI-906) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma: A double-blind, randomised, phase 3 study. Lancet Oncol 2015; 16: 426-435
    CrossrefPubMedGoogle Scholar
  • 20 Le DT, Durham JN, Smith KN. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017; 357: 409-413
    CrossrefPubMedGoogle Scholar
  • 21 Zhuang J, Wang D, Wu R. et al. Sunitinib monotherapy instead of mitotane combination therapy for the treatment of refractory adrenocortical carcinoma. Int J Urol 2015; 22: 1079-1081
    CrossrefPubMedGoogle Scholar
  • 22 Kroiss M, Megerle F, Kurlbaum M. et al. Objective response and prolonged disease control of advanced adrenocortical carcinoma with cabozantinib. J Clin Endocrinol Metab 2020; 105 dgz318
    PubMedGoogle Scholar
  • 23 Zheng S, Cherniack AD, Dewal N. et al. Comprehensive pan-genomic characterization of adrenocortical carcinoma. Cancer Cell 2016; 29: 723-736
    CrossrefPubMedGoogle Scholar
  • 24 Mariniello B, Rosato A, Zuccolotto G. et al. Combination of sorafenib and everolimus impacts therapeutically on adrenocortical tumor models. J Endocr Relat Cancer 2012; 19: 527
    CrossrefPubMedGoogle Scholar
  • 25 Angelousi A, Kyriakopoulos G, Nasiri-Ansari N. et al. The role of epithelial growth factors and insulin growth factors in the adrenal neoplasms. Ann Transl Med 2018; 6: 253
    CrossrefPubMedGoogle Scholar
  • 26 Miller KC, Chintakuntlawar AV, Hilger C. et al. Salvage therapy with multikinase inhibitors and immunotherapy in advanced adrenal cortical carcinoma. J Endocr Soc 2020; 4: bvaa069
    CrossrefPubMedGoogle Scholar
  • 27 Bedrose S, Miller KC, Altameemi L. et al. Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma. J Immunother Cancer 2020; 8: e001009
    CrossrefPubMedGoogle Scholar
  • 28 Kroiss M, Quinkler M, Johanssen S. et al. Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial. J Clin Endocrinol Metab 2012; 97: 3495-3503
    CrossrefPubMedGoogle Scholar
  • 29 Megerle F, Kroiss M, Hahner S. et al. Advanced Adrenocortical Carcinoma - What to do when First-Line Therapy Fails?. Exp Clin Endocrinol Diabetes 2019; 127: 109-116
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 30 Mota JM, Sousa LG, Braghiroli MI. et al. Pembrolizumab for metastatic adrenocortical carcinoma with high mutational burden: Two case reports. Medicine (Baltimore) 2018; 97: e13517
    CrossrefPubMedGoogle Scholar
  • 31 Caccese M, Ceccato F, Fassan M. et al. Letter to Editor: Reply to R.T. Casey (Semin Oncol 2018; 45: 151–155). Semin Oncol 2019; 46: 104-105
    CrossrefPubMedGoogle Scholar
  • 32 Nevgi A, Klein O, Cheung AS. Sustained remission of Lynch syndrome-associated metastatic adrenocortical carcinoma following checkpoint inhibitor therapy-associated multiorgan autoimmunity. Clin Endocrinol 2020; 93: 214-216
    CrossrefPubMedGoogle Scholar
  • 33 Gara SK, Lack J, Zhang L. et al. Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors. Nat Commun 2018; 9: 4172
    CrossrefPubMedGoogle Scholar
  • 34 Khoja L, Butler MO, Kang SP. et al. Pembrolizumab. J Immunother Cancer 2015; 3: 36
    CrossrefPubMedGoogle Scholar
  • 35 Naing A, Meric-Bernstam F, Stephen B. et al. Phase 2 study of pembrolizumab in patients with advanced rare cancers. J Immunother Cancer 2020; 8: e000347
    CrossrefPubMedGoogle Scholar
  • 36 Landwehr L-S, Altieri B, Schreiner J. et al. Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma. J Immunother Cancer 2020; 8: e000469
    CrossrefPubMedGoogle Scholar
  • 37 Raj N, Zheng Y, Kelly V. et al. PD-1 Blockade in Advanced Adrenocortical Carcinoma. J Clin Oncol 2020; 38: 71-80
    CrossrefPubMedGoogle Scholar
  • 38 Habra MA, Stephen B, Campbell M. et al. Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma. J Immunother Cancer 2019; 7: 253
    CrossrefPubMedGoogle Scholar
  • 39 Carneiro BA, Konda B, Costa RB. et al. Nivolumab in Metastatic Adrenocortical Carcinoma: Results of a Phase 2 Trial. J Clin Endocrinol Metab 2019; 104: 6193-6200
    CrossrefPubMedGoogle Scholar
  • 40 Le Tourneau C, Hoimes C, Zarwan C. et al. Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial. J Immunother Cancer 2018; 6: 111
    CrossrefPubMedGoogle Scholar
  • 41 Head L, Kiseljak-Vassiliades K, Clark TJ. et al. Response to Immunotherapy in Combination With Mitotane in Patients With Metastatic Adrenocortical Cancer. J Endocr Soc 2019; 3: 2295-2304
    CrossrefPubMedGoogle Scholar
  • 42 Andrews MC, Wargo JA. Immunotherapy resistance: the answers lie ahead - not in front - of us. J Immunother Cancer 2017; 5: 10
    CrossrefPubMedGoogle Scholar
  • 43 Puglisi S, Perotti P, Pia A. et al Adrenocortical Carcinoma with Hypercortisolism. Endocrinol Metab Clin North Am 2018; 47: 395-407
    CrossrefPubMedGoogle Scholar
  • 44 Kwok G, Yau TCC, Chiu JW. et al. Pembrolizumab (Keytruda). Hum Vaccin Immunother 2016; 12: 2777-2789
    CrossrefPubMedGoogle Scholar
  • 45 Markowitz JN, Fancher KM. Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. Pharmacotherapy 2018; 38: 357-369
    CrossrefPubMedGoogle Scholar
  • 46 Casey RT, Giger O, Seetho I. et al. Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab. Semin Oncol 2018; 45: 151-155
    CrossrefPubMedGoogle Scholar
  • 47 Crona J, Baudin E, Terzolo M. et al. ENSAT Registry-Based Randomized Clinical Trials for Adrenocortical Carcinoma. Eur J Endocrinol 2021; 184: R51-R59
    CrossrefPubMedGoogle Scholar