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ASCO 2015: Nivolumab Shows Highly Promising Activity in Advanced Liver Cancer

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Key Points

  • Of 42 evaluable patients with advanced hepatocellular carcinoma in a phase I/II study of nivolumab, eight (19%) responded with tumor reduction beyond 30%, with two having complete remissions.
  • Responses have been durable and surpassed 12 months in four patients as most patients continued on treatment.
  • Tumors stabilized in 48% of patients, with the longest case lasting beyond 17 months.
  • Overall survival rate at 12 months was 62%.

A phase I/II study testing the safety and antitumor activity of nivolumab (Opdivo) in advanced hepatocellular carcinoma has revealed one of the first signs that immunotherapy with immune checkpoint inhibitors will have a role in the treatment of liver cancer. The results and potential implications of the study were described by the lead author Anthony B. El-Khoueiry, MD, at a press conference at the 2015 ASCO Annual Meeting in Chicago (Abstract LBA101).

Dr. El-Khoueiry is Associate Professor of Clinical Medicine and Phase I Program Director at the University of Southern California Norris Comprehensive Cancer Center in Los Angeles. He will present more details on the study at the clinical science symposium on immunotherapy on Saturday, May 30.

Among 42 evaluable patients, 8 (19%) responded to the anti–PD-1 antibody with tumor reduction beyond 30%, with 2 having complete remissions. The responses have been durable with 50% lasting beyond 12 months as most patients continued on treatment. In addition, tumors stabilized in 48% of patients, with the longest case lasting beyond 17 months. The overall survival rate at 12 months was 62%.

Safe in Patients With Hepatitis

Seventy-five percent of the patients enrolled on the study had previously received systemic therapy, including 68% who had received sorafenib (Nexavar). Nivolumab was given intravenously every 2 weeks for up to 2 years.

Nivolumab was safe and well tolerated, even in patients with ongoing hepatitis B or C infections. Specifically, there have not been any safety concerns related to flares of hepatitis B infection or worsening viral infection. There were three different cohorts of patients, one with hepatitis B, one with hepatitis C, and one not infected with either hepatitis B or C. “The reason they were treated in separate cohorts was to ensure that nivolumab was safe in all these groups of patients. The dose was escalated separately in each group,” Dr. El-Khoueiry reported at the press conference. No maximum tolerated dose was defined in any of the three cohorts.

The majority of the side effects were mild to moderate in nature with rash among the most common. Abnormal liver enzymes and elevated amylase and lipase were also common, but were not accompanied by any significant clinical symptoms.

Breaking New Ground

“We are encouraged to see that nivolumab was safe overall, and the response rate as well as preliminary survival data look quite promising. While we have to verify this early signal in larger studies, this is one of the first signs that immunotherapy with immune checkpoint inhibitors will have a role in the treatment of liver cancer,” Dr. El-Khoueiry said. “While these results are preliminary and limited to a small number of patients, they remain exciting and provide strong justification for more studies of nivolumab and other immunotherapy approaches for patients with advanced liver cancer.”

“PD-1 immunotherapies continue to break new ground in diseases where nothing else seems to work well. The fact that this drug might stop advanced liver cancer in its tracks for months, even a year, is great news for patients,” ASCO Expert Lynn Schuchter, MD, FASCO, commented. “To understand the full impact of this approach, however, larger trials are needed.” Dr. Schuchter is the University of Pennsylvania’s C. Willard Robinson Professor of Hematology/Oncology, and Chief of the Hematology/Oncology Division and Program Leader for the Abramson Cancer Center’s Melanoma Research Program. She currently chairs ASCO’s Cancer Research Committee.

Leading Cause of Cancer Death Worldwide

Sorafenib is currently the only U.S. Food and Drug Administration–approved systemic treatment for advanced liver cancer, but just 2% of patients have an objective tumor response (more than 30% shrinkage) to sorafenib, and the average overall survival is 10 to 11 months.

About 35,660 patients will be diagnosed with liver cancer in the United States in 2015, but the disease is even more common in parts of Africa and Southeast Asia. Liver cancer is the leading cause of cancer death worldwide, accounting for more than 600,000 deaths each year.

This study received funding from Bristol-Myers Squibb.

Dr. El-Khoueiry reported honoraria from GlaxoSmithKline, Genentech/Roche, Bristol-Myers Squibb, Amgen, Exelixis, and AstraZeneca; a consulting or advisory role with GlaxoSmithKline, Genentech/Roche, Bristol-Myers Squibb, Amgen, Exelixis, and AstraZeneca; research funding from Astex Pharmaceuticals and Bristol-Myers Squibb (institutional); and travel, accommodations, and expenses from GlaxoSmithKline, Genentech/Roche, Bristol-Myers Squibb, Amgen, Exelixis, and AstraZeneca.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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