Objective To evaluate pooled prospective trial data investigating efficacy of systemic therapies in metastatic adrenocortical carcinoma (mACC), incorporating subgroup analyses by treatment modality and line, establishing survival and response benchmarks. Methods Prospective trials of systemic therapy regimens in mACC published from 2010 to July 2023 included. Primary endpoints were overall survival (OS), progression-free survival (PFS) and objective response rates (ORR). ORR was logit-transformed and pooled using a random effects model and inverse variance method. Kaplan-Meier curves for PFS and OS were digitised and summary curves were constructed using a multivariate extension of the DerSimonian-Laird method. Results Across twenty-four studies, 880 patients included: 386 received chemotherapy, 169 immunotherapy, 288 targeted therapy, and 37 other therapies. Treatment settings were first-line (383 patients, 44%), second-line or beyond (471, 54%), not reported (26, 3%). Pooled ORR was 9.0% (95% CI 6.0 – 13.2) with moderate heterogeneity (I 2 = 54.2%, P < 0.01). Subgroup analysis showed ORRs of 2.9% for targeted therapy, 12.3% for chemotherapy and 15.3% for immunotherapy. Pooled median OS was 9.9 months (95% CI 7.7 – 11.9) and pooled median PFS 2.6 months (95% CI 1.9 – 3.6). The 12-month OS rate was 41.6% (95% CI 33.1 – 51.2) and the 6-month PFS rate was 24.0% (95% CI 15.2 – 37.8). Conclusion This analysis establishes contemporary benchmarks for systemic treatments in mACC. While chemotherapy and immunotherapy offer modest survival benefits, the limited effectiveness of targeted therapy highlights the paucity of actionable molecular biomarkers. Future trials should aim to surpass the survival outcomes identified in this analysis.
Shekar et al. (Tue,) studied this question.