Phase 2 Trial of Single Agent Ipilimumab (Anti-CTLA-4) for Locally Advanced or Metastatic Pancreatic Adenocarcinoma
By R. Royal, Catherine L. Levy, Keli M. Turner, A. Mathur, M. Hughes, U. Kammula, R. Sherry, S. Topalian, Jie Yang, I. Lowy and 1 more. Journal of immunotherapy, 2010
1,107 citations recorded by the source corpus.
New, effective therapies are needed for pancreatic ductal adenocarcinoma. Ipilimumab can mediate an immunologic tumor regression in other histologies. This phase II trial evaluated the efficacy of Ipilimumab for advanced pancreatic cancer. Subjects were adults with locally advanced or metastatic pancreas adenocarcinoma with measurable disease, good performance status, and minimal comorbidities. Ipilimumab was administered intravenously (3.0 mg/kg every 3 wk; 4 doses/course) for a maximum of 2 courses. Response rate by response evaluation criteria in solid tumors criteria and toxicity were measured. Twenty-seven subjects were enrolled (metastatic disease: 20 and locally advanced: 7) with median age of 55 years (27 to 68 y) and good performance status (26 with Eastern Cooperative Oncology Group performance status =0 to 1). Three subjects experienced ≥ grade 3 immune-mediated adverse events (colitis:1, encephalitis:1, hypohysitis:1). There were no responders by response evaluation criteria in solid tumors criteria but a subject experienced a delayed response after initial progressive disease. In this subject, new metastases after 2 doses of Ipilimumab established progressive disease. But continued administration of the agent per protocol resulted in significant delayed regression of the primary lesion and 20 hepatic metastases. This was reflected in tumor markers normalization, and clinically significant improvement of performance status. Single agent Ipilimumab at 3.0 mg/kg/dose is ineffective for the treatment of advanced pancreas cancer. However, a significant delayed response in one subject of this trial suggests that immunotherapeutic approaches to pancreas cancer deserve further exploration.
Subfields: Epidemiology, Oncology
View Paper: https://www.semanticscholar.org/paper/1acc8443278979818bdaa4ebf5c216e75d0a6764
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Citations in the corpus
- Fibroblast heterogeneity in the cancer wound (2014, background): “Neoplastic cells undergo epigenetic and genetic changes resulting in a metastatic phenotype, and CAFs coevolve with the neoplastic cells during tumor progression by acquiring a proinflammatory gene expression pattern (Saadi et al., 2010).”
- The Pancreas Cancer Microenvironment (2012, neutral): “which may merit further investigation (103).”
- CSF1/CSF1R Blockade Reprograms Tumor-Infiltrating Macrophages and Improves Response to T Cell Checkpoint Immunotherapy in Pancreatic Cancer Models (2014, neutral): “Both programmed cell death protein 1 (PD1) and CTLA4 antagonists demonstrate limited ability to restrain PDAC growth in thismousemodel, similar to reported efficacy as single agents in patients with PDAC (3, 4).”
- Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer (2013, background): “In particular, patients with pancreatic ductal adenocarcinoma (PDA), the fourth most common cause of cancer-related deaths in the United States, had no objective responses to anti (α)-CTLA-4 (7) or α-PD-L1 monoclonal antibodies (5).”