Journal Article

Phase II study of neoadjuvant checkpoint blockade in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma

Ashleigh Guadagnolo, B., Hunt, Kelly K., Cormier, Janice N., Lin, Heather, Bishop, Andrew J., Bird, Justin, Lewis, Valerae O., Roland, Christina L., Keung, Emily Z., Patel, Shreyaskumar R., Wargo, Jennifer A., Somaiah, Neeta, Torres, Keila E., Lazar, Alexander J., Wang, Wei-Lien

2018

Overview

Background Soft tissue sarcomas are a heterogeneous and rare group of solid tumors of mesenchymal origin that can arise anywhere in the body. Although surgical resection is the mainstay of treatment for patients with localized disease, disease recurrence is common and 5-year overall survival is poor (~ 65%). Both radiation therapy and conventional chemotherapy are used to reduce local and distant recurrence. However, the utility of radiation therapy is often limited by disease location (in the case of retroperitoneal sarcomas, for instance) while systemic therapy with conventional lines of chemotherapy offer limited efficacy and are often poorly tolerated and associated with significant toxicity. Within the past decade, major advances have been made in the treatment of other malignancies including melanoma, renal cell carcinoma, and non-small cell lung carcinoma with the advent of immune-checkpoint inhibitors such as ipilimumab (anti-CTLA4), pembrolizumab (anti-PD1), and nivolumab (anti-PD1). The recently published SARC028 (NCT02301039), an open label, phase II, multicenter trial of pembrolizumab in patients with advanced bone and soft tissue sarcomas reported promising activity in select histologic subtypes of advanced STS, including undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. Methods There is a clear need for novel and effective adjuncts in the treatment of STS. We hypothesize that immune checkpoint blockade will be effective in patients with surgically resectable primary or locally recurrent dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma when administered in the neoadjuvant setting. The primary aim of this phase II, single-center, open label, randomized non-comparative trial is to determine the pathologic response to neoadjuvant nivolumab monotherapy and combination nivolumab/ipilimumab in patients with resectable dedifferentiated liposarcoma of the retroperitoneum or undifferentiated pleomorphic sarcoma of the trunk or extremity treated with concurrent standard of care neoadjuvant radiation therapy. Discussion This study will help define the role of single agent anti-PD1 and combination anti-CTLA4 and anti-PD1 therapy in patients with surgically resectable dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma. Trial registration ClinicalTrials.gov NCT03307616 , registered October 12, 2017.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Antineoplastic Agents, Immunological - pharmacology / Antineoplastic Agents, Immunological - therapeutic use / Biomedical and Life Sciences / Biomedicine / Biopsy / Bone cancer / Cancer patients / Cancer Research / Cancer therapies / Care and treatment / Chemotherapy / Clear cell-type renal cell carcinoma / Clinical Protocols / Cohort Studies / CTLA-4 protein / CTLA4 / Dosage and administration / Experimental therapeutics and drug development / Generalized linear models / Genomes / Health aspects / Health Promotion and Disease Prevention / Humans / Immune checkpoint inhibitors / Immunotherapy / Ipilimumab / Kidney cancer / Liposarcoma / Liposarcoma - drug therapy / Liposarcoma - pathology / Lung carcinoma / Medicine/Public Health / Melanoma / Mesenchyme / Metastasis / Microbiota / Molecular Targeted Therapy / Monoclonal antibodies / Neoadjuvant / Neoadjuvant Therapy / Neoplasm Grading / Neoplasm Staging / Nivolumab / Non-small cell lung carcinoma / Oncology / Patients / PD-1 protein / Pembrolizumab / Radiation therapy / Retroperitoneum / Sarcoma / Sarcoma - drug therapy / Sarcoma - pathology / Small cell lung carcinoma / Solid tumors / Study Protocol / Surgical Oncology / Targeted cancer therapy / Toxicity / Tumors