In a letter to The New England Journal of Medicine, Cecilia Söderberg-Nauclér, MD, PhD, and colleagues from the Karolinska Institutet, Stockholm, described experience with the anti-cytomegalovirus (CMV) agent valganciclovir (Valcyte) in the treatment of glioblastoma, citing dramatically improved overall survival that increased with increasing duration of treatment.1
CMV in Glioblastoma
In studying more than 250 cases of glioma, these investigators have found only 1 patient who was CMV-negative. Among 75 patients followed, median overall survival was 33 months in those with low-grade CMV infection and 13 months in those with high-grade CMV infection (P = .04), and 2-year overall survival was 63.6% vs 17.2% (P = .003), suggesting that CMV affects tumor progression.2
In the randomized VIGAS trial in 42 patients with glioblastoma performed by the investigators, valganciclovir treatment did not significantly reduce tumor growth, the primary endpoint of the study, at 3 and 6 months after surgery.3 However, an exploratory analysis showed that among 22 patients receiving at least 6 months of therapy, 2-year overall survival (50% vs 20.6%, P < .001) and median overall survival (24.1 vs 13.7 months, P = .003) were significantly increased compared with contemporary controls. Given these findings, 28 additional patients have been treated with compassionate-use valganciclovir in addition to standard therapy at Karolinska University Hospital.
Increased Overall Survival
Among the total of 50 patients treated with valganciclovir, 2-year overall survival was 62% compared with 18% among 137 contemporary controls with similar disease stage, surgical resection grade, and baseline treatment (P < .001), and median overall survival was 25.0 months vs 13.5 months (hazard ratio [HR] = 2.59, P < .001).
Among 40 patients who received at least 6 months of valganciclovir, 2-year overall survival was 70% and median overall survival was 30.1 months (HR = 3.20 vs controls, P < .001). Among 25 patients who received continuous valganciclovir treatment after the first 6 months, the 2-year overall survival rate was 90% and median overall survival was 56.4 months (HR = 5.52 vs controls, P < .001).
The authors stated, “It is unlikely that any bias in patient selection could have resulted in these high rates of survival. Our results highlight the need for a randomized trial targeting CMV in patients with glioblastomas.” ■
Disclosure: The study was supported by an independent investigational grant from Hoffmann–La Roche. For full disclosures of the study authors, visit www.nejm.org.
References
1. Söderberg-Nauclér C, Rahbar A, Stragliotto G: Survival in patients with glioblastoma receiving valganciclovir (correspondence). N Engl J Med 369:985-986, 2013.
2. Rahbar A, Orrego A, Peredo I, et al: Human cytomegalovirus infection levels in glioblastoma multiforme are of prognostic value for survival. J Clin Virol 57:36-42, 2013.
3. Stragliotto G, Rahbar A, Solberg NW, et al: Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: A randomized, double-blind, proof-of-concept study. Int J Cancer 133:1204-1213, 2013.
