Cancer Patients with Treated HCV Suitable for Chemo Trials

Harrys Torres, MD

Following their successful trial of direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection in patients with any cancer, investigators are calling on oncologists to include cancer patients with sustained virologic response (SVR) to HCV treatment among those eligible to participate in chemotherapy trials.

Harrys Torres, MD, Associate Professor of Medicine in the Department of Infectious Diseases, Infection Control and Employee Health and Adjunct Associate Professor, Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, Texas, and colleagues noted that despite increasing availability of safe and effective DAAs since 2013, the chemotherapy clinical trials that allow patients with chronic HCV infection have decreased from 54% in 2013 to 44% in 2018.

"Oncologists must work to change this picture as HCV infection alone is curable with DAA treatment in most cases," they wrote. "Chronic HCV infection should neither be considered a contraindication to investigational cancer treatment nor delay the initiation of an urgent cancer therapy."

"In our centers, most of our providers are concerned with the cancer and everything else is, sometimes, considered secondary," Torres told MD Magazine^®. "But when that secondary condition prevents enrolling the patient in clinical trials, it becomes a primary issue."

In their review of eligibility criteria of all phase 1-4 cancer clinical trials of chemotherapy or immunotherapy for adults at US sites registered in ClinicalTrials.gov from January 2013 to May 2018, Torres and colleagues found that of 5638 registered clinical trials meeting their review criteria, 2800 (50%) specifically excluded patients with chronic HCV infection, and another 258 (5%) were likely to exclude them for nonspecific criteria such as "chronic viral infection" and "chronic active or persistent hepatitis." A few—185 clinical trials (3%)—allowed participation of patients with chronic HCV infection if they had undetectable HCV RNA.

"We have to educate," Torres commented. "The issue here is most of our HepC treaters are familiar with the co-infected patient, with the drug use, with other populations, but with these patients, its really a niche. Many of our providers are not familiar with HepC patients with cancer."

Torres and colleagues described several beneficial outcomes from providing DAA treatment in cancer patients with chronic HCV infection in their call for improved HCV screening and access to DAA treatment, and for treated patients to be eligible for chemotherapy trials, including:

• Improved liver function and decreased portal pressure. They noted that this can facilitate access to cancer treatment, including liver surgery and locoregional therapy for primary liver cancer.
• Prevented HCV reactivation during cancer treatment. Torres and colleagues cited an observational study at their center in which 6 (26%) of 23 patients with HCV reactivation required unanticipated discontinuation or dose reduction of chemotherapy.
• Improved cancer treatment outcomes. The investigators described several studies that have found that chronic HCV infection reduces overall survival in patients with several types of cancer, and in hematopoietic cell transplant (HCT) recipients irrespective of other disease-related factors.
• Direct impact of DAA treatment on HCV-associated hepatic and extrahepatic malignancies. Torres and colleagues offer examples of patients with HCV-associated indolent lymphomas attaining complete or partial remission with DAA treatment alone. In addition, they note that patients with HCV-associated non-Hodgkin lymphoma who received antiviral therapy have had fewer cancer relapses after HCT than patients who did not receive antiviral therapy.

Torres and colleagues also provided several recommendations on coordinating DAA regimens for HCV with cancer treatment, including:

• DAA treatment should not be administered simultaneously with cancer treatment when potential drug-drug interactions are anticipated.
• Concomitant treatment should not be given when an overlap between the toxic effects of DAAs and cancer treatment is expected.
• When long-term cancer treatment is needed, DAAs can be used simultaneously and under close monitoring when potential drug-drug interactions with selected antineoplastic agents have been ruled out.
• Short duration (8-week vs 12-week) DAA regimens should be considered if the patient meets treatment criteria used in non-cancer patients.

"We prefer to use 8-week regimens, so we can treat the patients between (chemotherapy) cycles," Torres told MD Magazine^®. "The sooner we can finish, the better, so they can move on with the cancer care. Other potential benefits of the shorter regimen are less cost and less possible interactions with the cancer treatment."

Torres and colleagues conclude that, "in the DAA era, it is unacceptable to exclude cancer patients with chronic HCV infection from oncology clinic trials because of HCV alone. HCV-infected patients facing life-threatening malignancies should have access to investigational chemotherapy."

The report, “Hepatitis C Virus Infection in Patients with Cancer: Impact on Clinical Trial Enrollment, Selection of Therapy, and Prognosis,” was published in Gastroenterology.