PMID- 31276163 OWN - NLM STAT- MEDLINE DCOM- 20200604 LR - 20200604 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 104 IP - 12 DP - 2019 Dec 1 TI - Nivolumab in Metastatic Adrenocortical Carcinoma: Results of a Phase 2 Trial. PG - 6193-6200 LID - 10.1210/jc.2019-00600 [doi] AB - CONTEXT: Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest in checkpoint inhibitors such as anti-PD-1 nivolumab. OBJECTIVE: The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, and safety. DESIGN: Single-arm, multicenter, phase 2 clinical trial with two-stage design. SETTING: Comprehensive cancer center. PATIENTS: Ten adult patients with metastatic ACC previously treated with platinum-based chemotherapy and/or mitotane as well as patients who declined front-line chemotherapy. INTERVENTION: Nivolumab (240 mg) IV every 2 weeks. RESULTS: Ten patients with metastatic ACC were enrolled between March and December 2016. The median number of doses of nivolumab administered was two. Three patients only received one treatment [one died of disease progression, one discontinued due to adverse events (AEs), one withdrew after beginning treatment]. The median PFS was 1.8 months. The median follow-up was 4.5 months (range, 0.1 to 25.6 months). Two patients had stable disease for a duration of 48 and 11 weeks, respectively. One patient had an unconfirmed partial response but discontinued the study due to an AE. Most AEs were grade 1/2. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase and alanine aminotransferase elevations, mucositis, and odynophagia. CONCLUSION: Nivolumab demonstrated modest antitumor activity in patients with advanced ACC. The nivolumab safety profile was consistent with previous clinical experience without any unexpected AEs in this population. CI - Copyright (c) 2019 Endocrine Society. FAU - Carneiro, Benedito A AU - Carneiro BA AD - Developmental Therapeutics Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois. FAU - Konda, Bhavana AU - Konda B AD - Ohio State University Comprehensive Cancer Center, Columbus, Ohio. FAU - Costa, Rubens B AU - Costa RB AD - Developmental Therapeutics Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois. FAU - Costa, Ricardo L B AU - Costa RLB AD - Developmental Therapeutics Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois. FAU - Sagar, Vinay AU - Sagar V AD - Developmental Therapeutics Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois. AD - Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. FAU - Gursel, Demirkan B AU - Gursel DB AD - Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. FAU - Kirschner, Lawrence S AU - Kirschner LS AD - Ohio State University Comprehensive Cancer Center, Columbus, Ohio. FAU - Chae, Young Kwang AU - Chae YK AD - Developmental Therapeutics Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois. FAU - Abdulkadir, Sarki A AU - Abdulkadir SA AD - Developmental Therapeutics Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois. AD - Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. AD - Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. FAU - Rademaker, Alfred AU - Rademaker A AD - Department of Preventive Medicine, Northwestern University, Chicago, Illinois. FAU - Mahalingam, Devalingam AU - Mahalingam D AD - Developmental Therapeutics Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois. FAU - Shah, Manisha H AU - Shah MH AD - Ohio State University Comprehensive Cancer Center, Columbus, Ohio. FAU - Giles, Francis J AU - Giles FJ AD - Developmental Therapeutics Program, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois. LA - eng SI - ClinicalTrials.gov/NCT02720484 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Antineoplastic Agents, Immunological) RN - 31YO63LBSN (Nivolumab) SB - IM MH - Adrenal Cortex Neoplasms/*drug therapy/pathology MH - Adrenocortical Carcinoma/*drug therapy/secondary MH - Adult MH - Aged MH - Antineoplastic Agents, Immunological/*therapeutic use MH - Female MH - Follow-Up Studies MH - Humans MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Neoplasm Recurrence, Local/*drug therapy/pathology MH - Nivolumab/*therapeutic use MH - Prognosis MH - Survival Rate EDAT- 2019/07/06 06:00 MHDA- 2020/06/05 06:00 CRDT- 2019/07/06 06:00 PHST- 2019/03/13 00:00 [received] PHST- 2019/07/01 00:00 [accepted] PHST- 2019/07/06 06:00 [pubmed] PHST- 2020/06/05 06:00 [medline] PHST- 2019/07/06 06:00 [entrez] AID - 5528226 [pii] AID - 10.1210/jc.2019-00600 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2019 Dec 1;104(12):6193-6200. doi: 10.1210/jc.2019-00600.