38O - Clinical predictors of treatment response in advanced adrenocortical carcinoma: A multicentre ENSAT study

Background

Pharmacological treatment for advanced adrenocortical carcinoma (ACC) consists of mitotane alone or combined with cytotoxic chemotherapy. However, reliable predictors of response to therapy are lacking. We explored the predictive role of clinical parameters in a large cohort of patients with advanced ACC treated with systemic therapy.

Methods

We investigated a total of 439 patients with advanced ACC (62.6%=women, median age=52 years) from 11 European centres, treated with mitotane monotherapy (n=182), etoposide+cisplatin±doxorubicin±mitotane (EDP; n=178) or two different 2^nd-line chemotherapy schemes (gemcitabine+capecitabine±mitotane or temozolomide+mitotane n=79). Clinical parameters were collected at start of therapy including age, cortisol excess, ECOG-performance status (ECOG-PS), tumor burden (4 grades defined depending on size, number and site of metastasis), neutrophil-to-lymphocyte-ratio (NLR) and platelet-to-lymphocyte-ratio (PLR). Our endpoints were overall-survival (OS) and time-to-progression (TTP) from treatment initiation and best objective response to treatment according to RECIST 1.1 criteria.

Results

At multivariable analysis, tumour burden, cortisol excess, ECOG-PS and NLR≥5 significantly and independently predicted shorter OS and TTP in all cohorts (HR between 1.56 and 3.27). We calculated a combined BUCEN score as a sum of the following points: tumour BUrden (1=0, 2=1, 3/4=2), Cortisol excess (present=1), ECOG-PS (0=0, 1=1, 2/3=2), and NLR (≥5=1). A high BUCEN (≥3) resulted a significant predictor of short OS and TTP in all cohorts (mitotane cohort: OS HR= 4.08; 95%CI= 2.76-6.05; TTP HR=4.55; 95%CI= 2.99-6.91; EDP cohort: OS HR= 3.38; 95%CI= 2.22-5.14; TTP HR= 2.51; 95%CI= 1.62-3.89; 2^nd-line cohort: OS HR=3.96; 95%CI= 1.68-9.29; TTP HR= 3.10; 95%CI= 1.32-7.29). BUCEN≥3 also predicted best objective response to mitotane (p<0.01) and 2nd-line therapies (p=0.04), without reaching significance in the EDP cohort (p=0.06).

Conclusions

Our new proposed BUCEN score is a promising predictor of response to treatment in patients with advanced ACC and could be used to pre-select patients that could most benefit from systemic therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.