Lomustine with or without procarbazine in recurrent glioblastoma - A propensity score matching analysis
Tareq Haedenkamp, Anna Fischl, Michael Gerken, Tanja Rothhammer-Hampl, Amelie Fassbender, Verena Klein, Ilon Liu, Katharina Layer, Amani Suboh, Anna-Luisa Luger, Iris Mildenberger, Johannes Weller, Sied Kebir, Teresa Schmidt, Thomas Zeyen, Martin Glas, Ulrich Herrlinger, Julia Onken, Michael Platten, Friederike Schmidt-Graf, Joachim P Steinbach, Ralf Linker, Markus J Riemenschneider, Martin Proescholdt, Julia Maurer, Elisabeth Bumes, Peter HauAbstract
Background
Despite recent advances, survival in patients with glioblastoma remains poor. Outside clinical trials, lomustine is commonly considered standard of care in recurrent disease. However, comparative data between lomustine and other chemotherapy regimens are limited.
Methods
We performed a retrospective multicenter cohort study including patients from seven certified neuro-oncology centers in Germany to compare lomustine monotherapy with combination therapy using lomustine and procarbazine in first recurrence of glioblastoma. Propensity score matching was applied to obtain comparable groups based on sex, age, extent of resection at primary diagnosis, Karnofsky performance status at the start of recurrence therapy, and MGMT promoter methylation status. Post-recurrence survival (PRS) and progression-free survival (PFS) were analyzed using Kaplan–Meier estimation and multivariable Cox regression analysis.
Results
Seventy-seven patients were matched in each treatment group. PRS was comparable, with a median of 11.6 months for lomustine monotherapy and 10.0 months for lomustine plus procarbazine (log-rank test, p = 0.120). Multivariable Cox regression showed no significant difference (HR 1.33, 95% CI 0.93–1.90, p = 0.123). PFS was shorter in patients receiving combination therapy compared to monotherapy (3.7 vs. 5.1 months, log-rank test, p = 0.042). Multivariable Cox regression did not reveal significant differences (HR 1.31, 95% CI 0.90–1.90, p = 0.166).
Conclusions
Our data indicate that potential additive toxicity by intensified combination chemotherapy should be avoided due to lack of efficacy compared to lomustine monotherapy.