1. Neoadjuvant Immune Checkpoint Blockade in High-Risk Resectable Melanoma
- Author
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Neil D. Gross, Randal S. Weber, Wen-Jen Hwu, Jeffrey E. Lee, Shaojun Zhang, Courtney W. Hudgens, Vancheswaran Gopalakrishnan, Padmanee Sharma, Alexander J. Lazar, Rodabe N. Amaria, Merrick I. Ross, Amy C. Hessel, Christine N. Spencer, Lauren Simpson, Richard A. Ehlers, Jeffrey E. Gershenwald, Michael A. Davies, Michael K. Wong, Hussein Abdul-Hassan Tawbi, James P. Allison, Liberty Posada, Daniel K. Wells, Robin Kageyama, Sapna Pradyuman Patel, Isabella C. Glitza, Adi Diab, Denái R. Milton, Michael T. Tetzlaff, Richard E. Royal, Scott E. Woodman, Carol M. Lewis, Miles C. Andrews, Alexandre Reuben, Sangeetha M. Reddy, Lauren E. Haydu, Victor G. Prieto, Ehab Y. Hanna, Patrick Hwu, Elizabeth M. Burton, Janice N. Cormier, Jennifer A. Wargo, Anthony Lucci, Stephen Y. Lai, Jorge Blando, and Linghua Wang
- Subjects
0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,medicine.medical_treatment ,Phases of clinical research ,Ipilimumab ,General Biochemistry, Genetics and Molecular Biology ,Disease-Free Survival ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Melanoma ,Neoadjuvant therapy ,Neoplasm Staging ,business.industry ,General Medicine ,Immunotherapy ,Middle Aged ,medicine.disease ,Immune checkpoint ,Neoadjuvant Therapy ,3. Good health ,030104 developmental biology ,Nivolumab ,030220 oncology & carcinogenesis ,Female ,business ,Adjuvant ,medicine.drug - Abstract
Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses over adjuvant treatment1; however, optimal regimens have not been defined. Herein, we report results from a randomized phase II study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs), and immune correlates of response were assessed. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%) but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8% grade 3 trAEs). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. These results are the first to describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma and emphasize the need for additional studies to optimize treatment regimens and to validate putative biomarkers.
- Published
- 2018