Time Until Partial Response in Metastatic Adrenocortical Carcinoma Long-Term Survivors.

Delphine Vezzosi,Antoine Tabarin,Martin Schlumberger,Frédéric Illouz,Philippe Caron,Christine Do Cao,Vanina Bongard,Delphine Drui,Bodale Djobo,Sophie Leboulleux,Christelle De La Fouchardière,Claire Briet,Ségolène Hescot,Jérôme Bertherat,Françoise Borson‐Chazot ,R Libé ,A Berdelou ,M Haïssaguerre ,Éric Baudin

doi:10.1007/s12672-017-0313-6

Abstract

A partial response (PR) has been proposed as a surrogate for overall survival in advanced adrenocortical carcinoma (ACC). The primary endpoint of the study was to characterize the time until a PR in patients with metastatic ACC treated with a standard therapy is achieved. Long-term survivors were selected to allow evaluation of delayed tumor response to mitotane. Records from patients with metastatic ACC that survived for > 24months were retrieved. Tumor response was analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Time until a tumor response, after treatment initiation or therapeutic plasma mitotane level, was analyzed. Sixty-eight patients were analyzed. The first-line systemic therapy was mitotane as a monotherapy (M) (n=57) or cytotoxic polychemotherapy plus/minus mitotane (PC±M) (n=11). The second-line therapy was M (n=2) or PC±M (n=41). Thirty-two PRs occurred in 30/68 patients (44.1%): this was obtained for 13 (40.6%) during M and during PC±M for 19/32 responders (59.4%). PRs were observed within 6months of starting M or PC±M in 76.9 and 94.7% of responses, respectively, within 6months of therapeutic plasma mitotane being first observed in 88.9% of responses with M and in 53.3% of responses with PC±M. All PRs (but one) occurred within 1year after initiating treatment. To conclude, Most patients with metastatic ACC and long survival times had PRs within the first 6months of standard systemic therapy, and almost all within the first year. The absence of response after that period could be considered as a treatment failure. Maintenance of mitotane therapy in non-responders after 1year should be questioned in future randomized trials.

Highlights

The prognosis of patients with metastatic adrenocortical carcinoma (ACC) is usually poor with a survival time of less than 1.5 years [1, 2]; survival rates are heterogeneous [3,4,5]
Management of patients with metastatic ACC is based on expert opinions rather than results from phase III randomized trials
To provide our first insights into this critical question, the time until a partial response was analyzed in patients with advanced ACC and long-term survival rates, selected to take into account the delayed antitumor mitotane activity

Summary

Introduction

The prognosis of patients with metastatic adrenocortical carcinoma (ACC) is usually poor with a survival time of less than 1.5 years [1, 2]; survival rates are heterogeneous [3,4,5]. Mitotane plus local therapeutic options are recommended for patients that have favorable prognostic parameters, whereas polychemotherapy plus mitotane is recommended for those with unfavorable prognostic parameters [4]. In palliative care, partial responses to mitotane, when given as a monochemotherapy, have been reported in 13–33% of cases with response durations of 2– 190 months [5,6,7]. Partial response rates at the time of systemic polychemotherapy, combined or not with mitotane, have been reported in 11–30% of cases, with median durations of progression-free survival between 2 and 5 months

Methods

Results

Conclusion