The study also showed that chemotherapy disruption occurred in only 1.6% of patients  in the entecavir group compared to 18.3% for the lamivudine group.

Overall, the study showed that 24.6% of the entecavir-treated patients experienced treatment-related adverse events compared to 30.0% of the lamivudine-treated patients. 

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“There was one case of hepatic failure in the lamivudine group and none with entecavir,” Dr. Lin Told Cancer Therapy Advisor. “Therefore, entecavir is recommended as prophylactic antiviral treatment in [patients with] seropositive hepatitis B surface antigen cancer receiving chemotherapy.”

The researchers noted that entecavir is significantly more expensive than lamivudine, and so further studies are warranted to determine whether all patients seropositive for the hepatitis B surface antigen who receive rituximab-based immunosuppressive therapy should be given entecavir instead of lamivudine to prevent HBV flares. Jeremy Abramson, MD, of Harvard Medical School in Boston, MA, commented on the study findings in an accompanying editorial and believes a more nuanced approach may be possible.2

He said it may be that patients at low risk for HBV reactivation can be identified and preferentially followed up with surveillance alone. He said there are still also unanswered questions about the optimal duration of prophylactic antiviral therapy.

“This study only applies directly to patients with lymphoid malignancies receiving chemotherapy plus an anti-CD20 monoclonal antibody. Within this population, the findings of this study are sufficiently compelling as to consider prophylactic entecavir recommended standard prophylaxis in patients with positive HBV surface antigen undergoing chemoimmunotherapy. Targeted use of this therapy within this population likely would be cost effective,” Dr. Abramson told Cancer Therapy Advisor.

“Prior studies have shown entecavir to be cost effective compared to lamivudine in the treatment of active HBV, and in this population undergoing therapy 6-12 months of prophylaxis would likely prove cost effective despite the increased cost compared to lamivudine due to the cost savings associated with HBV reactivation, hepatitis, and delays in cancer therapy.”

Other cancer patients, including solid tumor patients, are also at increased risk of HBV reactivation. This is particularly true for patients with breast cancer who are undergoing anthracycline-containing therapy. However, their risk of reactivation is lower compared to patients with lymphoma receiving chemotherapy with anti-CD20 monoclonal antibodies.

“Whether entecavir is superior to lamivudine in [patients with breast cancer] remains uncertain, but given the superiority in other settings versus lamivudine, entecavir would still be my first choice for prophylaxis in all [patients with] cancer with positive HBV surface antigen undergoing chemotherapy.”

Francisco Hernandez-Ilizaliturri, MD, of Roswell Park Cancer Institute in Buffalo, NY, said the findings confirmed the long-postulated hypothesis that stronger antiviral medications may be more effective in preventing hepatitis B reactivation during rituximab-based chemo-immunotherapy.

RELATED: Hepatitis B Screening Urged for Patients Undergoing Chemo, Immunotherapy

“The results of this study are most likely to change current practice in institutions that use lamivudine prophylaxis in cancer patients coinfected with the hepatitis B virus. In addition, the results of this study may be extrapolated to other vulnerable patient populations co-infected with HBV and receiving rituximab-based therapies, such as those with other B-cell lymphoid malignancies or autoimmune disorders,” Dr. Hernandez-Ilizaliturri told Cancer Therapy Advisor.

Additional studies evaluating the efficacy and safety of entecavir to prevent HBV reactivation in patients with non-hematological cancer receiving chemotherapy with or without monoclonal antibodies targeting cancer-associated antigens are warranted.


  1. Huang H, Li X, Zhu J, et al. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA. 2014;312(23):2521-2530.
  2. Abramson JS, Chung RT. Optimal antiviral prophylaxis against hepatitis B reactivation in patients receiving rituximab-based chemotherapy for lymphoma. JAMA. 2014;312 (23):2505-2507.