Endocrine Abstracts

Introduction: After progression on conventional treatment options, some patients with advanced ACC are offered experimental Phase I therapies. The outcomes of these patients have not yet been formally evaluated. This study aims to describe the experience of refractory ACC patients treated on Phase I clinical trials at the RMH.

Methods: We retrospectively reviewed the records of metastatic ACC patients consecutively treated in our Drug Development Unit between January-2003 and December-2014.

Results: Sixteen patients (43.8% males) with median age of 45 years (23–62) were treated on 24 Phase I clinical encounters: 18 (75%) patients received targeted therapy (55.5% insulin-like growth factor pathway inhibitors), 3 (12.5%) chemotherapy and 3 (12.5%) chemotherapy combined with targeted agents. Overall response rate was 8.4% and clinical benefit rates at 4 and 6 months were 37.5% and 8.4%, respectively. Median progression-free survival and overall survival (OS) were 3.1 months (95% CI, 1.7–4.4) and 7.2 months (95% CI, 4.2–20.8), respectively. ECOG PS 1 versus 0 (P=0.009), >2 metastatic sites (P<0.001), peritoneal metastases (P=0.016), high platelet count (≥410×10⁹/l) (P=0.014), albumin <35 g/dl (P=0.026) and elevated LDH (P=0.019) were significantly associated with shorter OS. Patients with RMH score 0–1 (good prognosis) had superior median OS (14.1 months, 95% CI, 7.8–24.8) than those with a score 2–3 (bad prognosis) (5 months; 95% CI, 3.5–6.6) (P=0.001). Three (18.8%) patients experienced drug-related grade 3–4 toxicities. There were no toxicity-related treatment discontinuations or deaths.

Conclusions: Phase I clinical trials can be considered a reasonable therapeutic approach for ACC patients who failed conventional treatments due to low risk of toxicity and the potential for clinical benefit. The RMH prognostic score can help to identify patients most likely to benefit from these investigational agents.