Impact of EDP-M on survival of patients with metastatic adrenocortical carcinoma: A population-based study

Pien Debets; Koen M A Dreijerink; Anton Engelsman; Max Dahele; Harm R Haak; Rebecca V Steenaard; Ellen Kapiteijn; Eleonora Corssmit; C Willemien Menke-van der Houven van Oordt

doi:10.1016/j.ejca.2023.113424

Impact of EDP-M on survival of patients with metastatic adrenocortical carcinoma: A population-based study

Eur J Cancer. 2024 Jan:196:113424. doi: 10.1016/j.ejca.2023.113424. Epub 2023 Nov 10.

Authors

Pien Debets¹, Koen M A Dreijerink², Anton Engelsman³, Max Dahele⁴, Harm R Haak⁵, Rebecca V Steenaard⁶, Ellen Kapiteijn⁷, Eleonora Corssmit⁸, C Willemien Menke-van der Houven van Oordt⁹

Affiliations

¹ Amsterdam UMC location VU Medical Center, department of Medical Oncology, Amsterdam, the Netherlands.
² Amsterdam UMC location VU Medical Center, department of Endocrinology and Metabolism, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands.
³ Amsterdam UMC location VU Medical Center, department of Surgery, Amsterdam, the Netherlands.
⁴ Amsterdam UMC location VU Medical Center, Department of Radiation Oncology and Cancer Center Amsterdam, Amsterdam, the Netherlands.
⁵ Maxima Medical Center, department of Internal Medicine, Eindhoven, the Netherlands; Maastricht University, CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht, the Netherlands; Department of Internal Medicine, Division of General Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands.
⁶ Maxima Medical Center, department of Internal Medicine, Eindhoven, the Netherlands; Maastricht University, CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht, the Netherlands; Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands.
⁷ Leiden University Medical Center, Department of Medical Oncology, Leiden, the Netherlands.
⁸ Leiden University Medical Center, Center of Endocrine Tumours, Division of Endocrinology, Department of Internal Medicine, Leiden, the Netherlands.
⁹ Amsterdam UMC location VU Medical Center, department of Medical Oncology, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands. Electronic address: c.menke@amsterdamumc.nl.

PMID: 37977106
DOI: 10.1016/j.ejca.2023.113424

Abstract

Introduction: Historically, stage IV adrenocortical carcinoma (mACC) has a poor prognosis with a median overall survival (OS) of only 5 months. Based on the FIRM-ACT trial published in 2012, guidelines now advise first line systemic treatment with etoposide, cisplatin, doxorubicin and mitotane (EDP-M). The effect of EDP-M on patient survival in clinical practice in the Netherlands is unknown.

Methods: The data of all patients with mACC (2005-2020) were obtained from the Netherlands comprehensive cancer organization (IKNL). The effect of EDP-M on patient survival was assessed using Kaplan-Meier analysis and multivariate Cox regression analysis including clinical, therapy and tumor characteristics.

Results: In total 167 patients with mACC were included. For patients diagnosed from 2014 onwards, EDP-M (in 22 patients (22%)) lead to a numerically but not statistically significant improved OS compared to those not receiving EDP-M (11.8 vs 5.6 months, p = 0.525). For systemic treatments, patients treated with mitotane only had the best 5-year OS (11.4%, p = 0.006) regardless of year of diagnosis. In multivariate Cox regression analysis EPD-M was not associated with OS; palliative adrenalectomy (HR: 0.26, p = <.001) and local treatment of metastases (HR: 0.35, p = 0.001) were associated with a better OS and a primary tumor Ki-67 index > 20% (HR: 2.67, p = 0.003) with a worse OS from 2014 onwards. Patients diagnosed before 2014 had a significantly poorer OS compared to from 2014 onwards (5-yr: 4.5 vs 8.4%, OS: 6.8 vs 8.3 months, p = 0.032).

Conclusion: OS for mACC in the Netherlands has improved in the last decade. Receiving EDP-M did not significantly improve OS for patients with mACC. The use of multimodality treatment including palliative adrenalectomy, mitotane and local treatment of (oligo-)metastases in appropriately selected patients has improved the OS for mACC patients since 2014.

Keywords: Chemotherapy; Metastatic adrenocortical carcinoma; Mitotane; Palliative adrenalectomy; Survival analysis.

MeSH terms

Adrenal Cortex Neoplasms* / drug therapy
Adrenocortical Carcinoma* / drug therapy
Adrenocortical Carcinoma* / etiology
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cisplatin
Etoposide
Humans
Mitotane / adverse effects
Mitotane / therapeutic use

Substances

Mitotane
Etoposide
Cisplatin