Valganciclovir Improves Survival in Patients with Glioblastoma
ABSTRACT & COMMENTARY
By Richard R. Watkins, MD, MS, FACP
Division of Infectious Diseases, Akron General Medical Center, Akron, OH; Associate Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH
Dr. Watkins reports no financial relationships in this field of study.
SOURCE: Soderberg-Naucler C, et al. Survival in patients with glioblastoma receiving valganciclovir. N Eng J Med 2013;369:985-986.
Glioblastoma is one of the most aggressive solid tumors, with a median overall survival of 12 to 14 months and a two-year survival of 15% to 26% despite our best current therapies. Recently it has been suggested that cytomegalovirus (CMV) acts as a tumor promoter in breast cancer.1 CMV is a very common infection in humans and has a seroprevalence rate of at least 50% in the U.S.2 Investigators from Sweden sought to determine the prevalence of CMV in patients with glioblastoma and elucidate what effect valganciclovir might have on disease progression and survival.
Soderberg-Naucler and colleagues examined 250 cases of glioblastoma and all but one were CMV-positive. Of the 75 patients they further evaluated, the median survival rate was 33 months in those with low-grade CMV infection compared to 13 months in those with high-grade CMV infection (P=0.04). Using data from a double-blind clinical trial or a compassionate-use program at their institution, the investigators found two-year survival was 62% among 50 patients who received valganciclovir in addition to standard therapy compared to 18% of controls who did not receive valganciclovir (P<0.001).
The two groups were matched for disease stage, surgical-resection grade, and baseline treatment.Overall, the median survival was 25 months in the patients who received valganciclovir and 13.5 months in those who did not (P<0.001). Furthermore, in a subgroup analysis the median two-year survival of patients who received valganciclovir for at least 6 months was 70%, while those who received continuous valganciclovir after the first 6 months had a two-year survival of 90% (P<0.001). The median survival in this latter group was 56.4 months.
The results of this study and their possible clinical implications are profound given the dismal prognosis associated with glioblastoma. Indeed, such high survival rates have never been reported in previous studies. Although its high incidence in tumors has been appreciated for several years, many experts have dismissed CMV as a bystander and not a promoter of disease.
Enthusiasm for the findings of the present study must be somewhat mitigated by its limitations. First, it had a retrospective design, a small sample size, and was conducted at a single institution. Second, no information was provided about side-effects of the medication, specifics about the diagnosis of CMV, nor if those patients with increased survival had measurable improvement in their CMV viral indices. Third, there was no explanation why certain patients received a longer duration of therapy than others. Finally, while the authors suggested it was unlikely selection bias could have accounted for the high survival rates, this cannot be ascertained with a reasonable degree of certainty without a more detailed description of the study population.
While the results of this single study are impressive, they are preliminary and should be the impetus for additional multicenter, prospective trials. One important question still unanswered is which patients with glioblastoma and CMV should be treated? Should it be all of them or only those expected to survive at least 6 months to a year? Until more data are available, the routine use of valganciclovir for glioblastoma can not be recommended. The potential role of immunotherapy, such as a CMV vaccine, in the treatment of glioblastoma also requires further investigation.
- Taher C, et al. High prevalence of human cytomegalovirus proteins and nucleic acids in primary breast cancer and metastatic sentinel lymph nodes. PloS One 2013;8:e56795.
- Bate SL, et al. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004. Clin Infect Dis 2010;50:1439-1447.