P17.13.A OUTCOME ANALYSIS OF PATIENTS WITH RECURRENT HIGH-GRADE GLIOMAS TREATED WITH ORAL ETOPOSIDE (VP16) IN ALBERTA, CANADA: A POPULATION-BASED RETROSPECTIVE STUDY
Authors: Gao Y , Lim C , Ghosh S , Folkman F , Roldan Urgoiti G 
Published: September 2023

Abstract

BACKGROUND
Tumour recurrence in patients with gliomas is associated with short survival and there is no standard second-line therapy. Etoposide (VP16) taken orally is one of the systemic treatment options available with an acceptable safety profile in this patient population.

MATERIAL AND METHODS
We conducted a retrospective analysis of patients who received oral VP16 as monotherapy for the management of recurrent/progressive gliomas in Alberta, Canada 2009 - 2019 with the aim to identify the patients’ clinical and histological characteristics associated with improved outcomes with VP16. Eligible patients were identified using the provincial pharmacy records. As progression free survival (PFS) in second line treatment in these patients is &lt; 3 months we defined as “benefiting” from VP16 those patients that completed 4 or more cycles/months of VP16. Two-tailed χ2 or Fisher’s exact tests were used to determine the significance of associations between proportions. Cox proportional hazards model and Kaplan-Meier survival analysis with log-rank test were used to determine factors associated with Overall Survival (OS) and PFS.

RESULTS
At the time of current abstract, data abstraction was completed for 200 out of 350 identified patients. Partial data analysis were performed on 197 patients who received at least one cycle of VP16 for recurrent glioma; 55 patients (28%) completed 4 or more cycles of VP16; patients with oligodendroglioma were 60% more likely to benefit while patients with glioblastoma were 1.56 times more likely to stop before 4 months of treatment. Patients that received 4 or more cycles of VP16 were younger (p=0.041); compared to patients &gt; 61 years old, patients 21-31 and 41-61 years old were 82% and 29% less likely to stop before cycle 4, respectively (OR 0.18 and 0.71). Median OS from diagnoses for patients that did not benefit from VP16 was 22 (95% CI; 15.7 to 28.3) months compared to 45.7 (95% CI; 31.8 to 59.5) months in patients that were able to receive at least 4 cycles of VP16 (p=0.006). However, the proportion IDH mutated tumors, MGMT promoter methylation and use of dexamethasone at start of treatment did not differ between patients that benefit or not from VP16. As expected, lower KPS (p=0.007) and diagnoses of glioblastoma (p=0.001) were associated with worse OS. Better OS and PFS were associated with MGMT promoter methylation (p&lt;0.0001 and p=0.030, respectively), 1p/19q codel (p=0.042 and p=0.018, respectively), and IDH mutation status (p&lt;0.0001 and p=0.022, respectively).

CONCLUSION
In this retrospective series of patients with recurrent gliomas that started VP16 more than 1/4 of the patients received 4 or more cycles/months of treatment. Younger patients and those with oligodendrogliomas were more likely to benefit. We consider VP16 at 50 mg/day po a valid option for patients whose performance status would allow trying an additional line of palliative systemic treatment.