Subscribe

Nivolumab Makes Headwinds into Liver Cancer

August 2015 Vol 8, Special Issue: Payers' Perspectives in Oncology - Emerging Therapies
Wayne Kuznar

Immunotherapy with nivolumab resulted in durable responses and promising overall survival (OS) in a dose-escalation and expansion trial of patients with advanced liver cancer. The 12-month OS rate exceeded 60% in patients in whom sorafenib had failed, and responses occurred in patients with the hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, reported Anthony B. El-Khoueiry, MD, Norris Comprehensive Cancer Center, Los Angeles, at ASCO 2015.

“Sorafenib remains the only standard-of-care systemic therapy for patients with advanced hepatocellular carcinoma, with median survival limited to <11 months,” said Dr El-Khoueiry. “Patients who progress on sorafenib have no standard-of-care second-line therapy options. Based on recently completed phase 3 trials in the setting of sorafenib failure, the median survival with best supportive care is approximately 7 to 8 months.”

Hepatocellular carcinoma is typically an inflammation-associated cancer that can be immunogenic. Furthermore, HCV infection and HBV infection have been associated with the upregulation of PD-1. The upregulation of PD-1 and its ligand 1 (PD-L1) have been associated with worse prognosis in hepatocellular carcinoma, especially after resection or ablation.

In the phase 1/2 study, nivolumab was evaluated in patients enrolled in dose escalation in 2 parallel cohorts—patients with HBV or HCV and uninfected patients. Dose escalation was followed by ongoing dose expansion. Patients were permitted ≥1 lines of previous systemic therapy, including sorafenib.

Overall, 47 patients were evaluable for safety (43 from the dose-escalation phase and 4 from the dose-expansion phase) at the time of the interim analysis presented at ASCO 2015. A maximum tolerated dose was not defined, and drug-related adverse events occurred in 68% of patients, with 19% being grade 3 or 4.

Currently, 17 patients remain in the study; a total of 30 patients discontinued treatment, with 26 discontinuations resulting from disease progression, 2 from drug-related adverse events, and 2 from achieving a complete response.

Of 42 patients who were evaluable for response, 8 (19%) had an objective response (5% had a complete response and 14% had a partial response). In all, 48% of the patients had stable disease.

Responses occurred across all the etiologic cohorts. “In addition to the confirmed responses,…40% of patients had some reduction in the size of their tumors,” said Dr El-Khoueiry. Among the 8 responders, 7 had responses lasting >9 months, and responses are on­going in 6 patients. Of the 8 patients who responded, 7 did so within 3 months of beginning treatment.

The OS rate at 12 months is 62%. “To put this in context, the 12-month OS rate after sorafenib failure, based on recently completed phase 3 trials, is about 30%,” Dr El-Khoueiry said.

“The durable responses and prolonged stable diseases, along with the encouraging 12-month OS, lend strong support to the ongoing dose-expansion phase of the study to validate the promising signal and for continued exploration of nivolumab in hepatocellular carcinoma,” Dr El-Khoueiry concluded.

Related Items
Advances in Cellular Therapies for Hematologic Malignancies Highlighted at ASH 2019
Wayne Kuznar
February 2020 Vol 13, Special Issue published on February 25, 2020 in Conference Highlights ASH
Mosunetuzumab, a Dual-Targeted Antibody, Shows Complete Remissions in Relapsed/Refractory NHL After CAR T-Cell Therapy
Phoebe Starr
February 2020 Vol 13, Special Issue published on February 25, 2020 in Emerging Therapies
Apamistamab-Based Lymphodepleting Regimen Before CAR T-Cell Therapy May Prevent Cytokine Release Syndrome
Wayne Kuznar
February 2020 Vol 13, Special Issue published on February 25, 2020 in Emerging Therapies
First-Line Acalabrutinib-Based Triplet Therapy Leads to Undetectable Minimal Residual Disease in CLL
Wayne Kuznar
February 2020 Vol 13, Special Issue published on February 25, 2020 in Leukemia
Investigational Oral Form of Azacitidine Improves Survival Maintenance Therapy in Patients with Acute Myeloid Leukemia
Wayne Kuznar
February 2020 Vol 13, Special Issue published on February 25, 2020 in Leukemia
Last modified: September 14, 2015
Copyright © Engage Healthcare Communications, LLC. All rights reserved.