3P Beyond first-line therapy in metastatic adrenal cortical cancer (ACC): Is it time to move on from chemotherapy?

Abstract

Metastatic ACC is a rare and aggressive tumor with limited treatment options beyond first-line chemotherapy. Unfortunately, survival outcomes are poor with 2nd line chemotherapy, which is frequently adopted for treatment. Data on outcomes with non-chemotherapeutic approaches including immunotherapy is scarce. A retrospective review (2002-2020) of metastatic ACC patients treated at Princess Margaret Cancer Center was performed. Patients who received any 2nd line therapy and beyond were identified. Descriptive statistics were used to summarize clinical and demographic data. Progression free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Survival outcomes were compared using log-rank test. Out of 84 patients with metastatic ACC, 30 (20.7%) had de novo and 54 (37.2%) recurrent disease after local definitive therapy; 51 (60.7%) and 30 (58.8%) received 1st and 2nd line systemic therapy respectively. Median age was 49 years (36-58); 18 (60%) were female,14 (47%) had functional tumors, 4 (13.3%), 25 (83.3%), and 1 (3.3%) were ECOG 0, 1 and 2 respectively. One patient had MMR deficiency out of 16 patients in which it was evaluated. Seventeen patients (56.6%) received chemotherapy (14-gemcitabine capecitabine, 1-gemcitabine, 2-etoposide doxorubicin and cisplatin rechallenge) and 13 patients (43.4%) received non chemotherapy treatment (8- clinical trial, 4-sunitinib, 1-pembrolizumab ). Mitotane was continued in 16 of 22 (72.7%) patients for which data was available. Baseline characteristics and disease control rate were similar between the two groups (18% for chemotherapy vs 31% for non -chemotherapy, p=0.46). Median PFS was similar (2.6 months (2-4) and 3 months (1.7-4.5), p=0.48), however OS was numerically better with non- chemotherapy (6.6 months (4.9-13.1) vs 10.2 months (5.9-22.7) p=0.08. This study shows favorable outcomes with non-chemotherapy approaches compared to chemotherapy. Although this needs to be confirmed in larger studies, given the lack of randomized data for superiority of chemotherapy, non-chemotherapy approaches including immunotherapy and clinical trials should be considered where appropriate.