Endocrine Abstracts

Background: Treatment for advanced adrenocortical carcinoma (ACC) consists of mitotane alone or combined with etoposide, doxorubicin and cisplatin (EDP), yet their efficacy is limited and burdened with significant toxicity. Moreover, markers of response are lacking. Inflammation-based scores have been proposed as prognostic factors in several malignancies including ACC, and recently also as predictors of gemcitabine+capecitabine efficacy, second-line treatment in progressive disease. We therefore investigated the role of inflammation-based scores in predicting response to first-line therapy in advanced ACC.

Methods: We performed a retrospective analysis of patients with advanced ACC treated with mitotane alone or EDP±mitotane in two European centres. We investigated clinical parameters (tumour stage at diagnosis, resection status, Ki67 index, time from diagnosis to treatment start, performance status, plasma mitotane levels, time in mitotane target ≥80%, cortisol hypersecretion at treatment initiation) and pre-treatment inflammation-based scores [neutrophil-to-lymphocyte-ratio (NLR), platelet-to-lymphocyte-ratio (PLR), monocyte-to-lymphocyte-ratio (MLR), derived neutrophil-to-lymphocyte ratio (dNLR), serum albumin]. Primary and secondary endpoints were overall-survival (OS) and time-to-progression (TTP) from treatment initiation, respectively. We additionally evaluated the best objective response to treatment, defined according to RECIST 1.1 criteria.

Results: We included 90 eligible patients (59% women, median age: 51 years) treated with mitotane monotherapy (n=40) or EDP±mitotane (n=50). In the mitotane cohort, NLR≥5 and PLR≥190 predicted shorter OS (HR: 145.83, 95%CI: 1.87-11323.83, P=0.025; HR: 165.50, 95%CI: 1.76-15538.04, P=0.0027, respectively), remaining significant at Cox regression multivariable analysis including resection status, time from diagnosis to start treatment, ECOG performance status, cortisol hypersecretion and time in mitotane target. NLR was also associated with shorter TTP (HR: 2.58, 95%CI: 1.28-5.20, P=0.008), but only at univariable analysis. Patients with NLR≥5 showed a worse response to mitotane than those with NLR<5 (P=0.040). In the EDP cohort, NLR≥5 predicted shorter OS (HR: 2.52, 95%CI: 1.30-4.88, P=0.006) and TTP (HR: 1.95, 95%CI: 1.04-3.66, P=0.037), which was not confirmed at multivariable analysis.

Conclusion: Inflammation-based scores, calculated from routinely measured parameters, may help predict response to first-line pharmacotherapy in advanced ACC. These findings will be validated in larger cohorts.