PD-1 blockade in advanced adrenocortical carcinoma Journal Article
| Authors: | Raj, N.; Zheng, Y.; Kelly, V.; Katz, S. S.; Chou, J.; Do, R. K. G.; Capanu, M.; Zamarin, D.; Saltz, L. B.; Ariyan, C. E.; Untch, B. R.; O’Reilly, E. M.; Gopalan, A.; Berger, M. F.; Olino, K.; Segal, N. H.; Reidy-Lagunes, D. L. |
| Article Title: | PD-1 blockade in advanced adrenocortical carcinoma |
| Abstract: | PURPOSE Adrenocortical carcinomas (ACC) are rare and aggressive malignancies with limited treatment options. This study was undertaken to evaluate the immunogenicity of ACC. PATIENTS AND METHODS Patients with advanced ACC were enrolled in a phase II study to evaluate the clinical activity of pembrolizumab 200 mg every 3 weeks, without restriction on prior therapy. The primary end point was objective response rate. Efficacy was correlated with tumor programmed death-ligand 1 expression, microsatellite-high and/or mismatch repair deficient (MSI-H/MMR-D) status, and somatic and germline genomic correlates. RESULTS We enrolled 39 patients with advanced ACC and herein report after a median follow-up of 17.8 months (range, 5.4 months to 34.7 months). The objective response rate to pembrolizumab was 23% (nine patients; 95% CI, 11% to 39%), and the disease control rate was 52% (16 patients; 95% CI, 33% to 69%). The median duration of response was not reached (lower 95% CI, 4.1 months). Two of six patients with MSI-H/MMR-D tumors responded. The other seven patients with objective responses had microsatellite stable tumors. The median progression-free survival was 2.1 months (95% CI, 2.0 months to 10.7 months), and the median overall survival was 24.9 months (95% CI, 4.2 months to not reached). Thirteen percent of patients (n = 5) had treatment-related grade 3 or 4 adverse events. Tumor programmed death-ligand 1 expression and MSI-H/MMR-D status were not associated with objective response. CONCLUSION MSI-H/MMR-D tumors, for which pembrolizumab is a standard therapy, are more common in ACC than has been recognized. In advanced ACC that is microsatellite stable, pembrolizumab provided clinically meaningful and durable antitumor activity with a manageable safety profile. © 2019 by American Society of Clinical Oncology |
| Keywords: | adult; clinical article; protein expression; aged; overall survival; somatic mutation; constipation; drug tolerability; fatigue; neutropenia; advanced cancer; diarrhea; drug efficacy; drug safety; hypophosphatemia; treatment duration; nuclear magnetic resonance imaging; follow up; anorexia; tumor associated leukocyte; cancer immunotherapy; edema; progression free survival; pain; phase 2 clinical trial; anemia; mucosa inflammation; nausea; vomiting; libido disorder; creatinine; creatinine blood level; adrenal cortex carcinoma; alanine aminotransferase blood level; aspartate aminotransferase blood level; chill; dizziness; fever; hyperglycemia; hypomagnesemia; lymphocytopenia; pneumonia; pruritus; rash; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; hypoalbuminemia; hypokalemia; hyponatremia; malaise; mismatch repair; peripheral edema; hyperpigmentation; skin disease; alkaline phosphatase blood level; heterozygosity loss; hyperthyroidism; hypothyroidism; cancer control; dry eye; dry skin; alopecia; bilirubin blood level; disease exacerbation; hypocalcemia; programmed death 1 ligand 1; conjunctivitis; germline mutation; next generation sequencing; tumor immunogenicity; human; male; female; priority journal; article; pembrolizumab; treatment interruption; duodenitis; treatment response time |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 38 |
| Issue: | 1 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2020-01-01 |
| Start Page: | 71 |
| End Page: | 80 |
| Language: | English |
| DOI: | 10.1200/jco.19.01586 |
| PUBMED: | 31644329 |
| PROVIDER: | scopus |
| PMCID: | PMC7351334 |
| DOI/URL: | |
| Notes: | Source: Scopus |
