Neurocognitive Functioning and Quality of Life in Patients with Recurrent Glioblastoma Treated with Avelumab and Axitinib

Glioblastoma is the most frequent malignant tumor of the central nervous system. After surgery, temozolomide chemotherapy and radiation therapy, the cancer almost inevitably recurs. Patients with recurrent glioblastoma (recGB) have a median overall survival of 25 to 30 weeks. Up till now, randomized clinical trials have not demonstrated any treatment option to improve the overall survival expectancy of patients with recGB. In this study, axitinib, a small molecule tyrosine kinase inhibitor of the VEGFReceptor, and avelumab, a monoclonal antibody directed against PD-L1, are being combined to treat recGB. The primary objective is to assess the anti-tumor effect of this combination therapy and to document the percentage of patients who are alive and confirmed free from tumor progression at 24 weeks. An important secondary objective is to assess neuro-cognitive functioning (NCF), psycho-emotional wellbeing and quality of life (Qol) in the patients.
Patients with recGB following prior treatment with surgery, radiation therapy and temozolomide chemotherapy are stratified to stratum A “no need for corticosteroids” or stratum B “baseline need for steroid treatment”. Anti-tumor activity is assessed with an MRI every 6 weeks. NCF testing is monitored by the Cogstate test battery at baseline (week 1, before start of treatment), at week 9 and every 12 weeks thereafter. On that same time schedule, some questionnaires will be administered to evaluate Qol, history of personal and/or familial psychiatric disorders, sleep disturbances and subjective cognitive symptoms: (1) Hospital Anxiety and Depression Scale (HADS), (2) EORTC Quality of Life Questionnaire (QLQ-C30), (3) EORTC Brain Cancer module (QLQ-BN20), (4) Anamnestic Comparative Self-Assessment (ACSA).
Descriptives of the baseline measurements (n = 17) of this ongoing study learn that fatigue was reported most frequently (68.75%) as the most disabling symptom. This is reflected in the QLQ-C30 fatigue score (M = 54.52, SD = 29.37), but not in the insomnia score (M = 20.83, SD = 29,50). With a cut-off score = 11, the HADS indicated that 23.5% of the patients seem to suffer from anxiety (Mdn = 6, Q1 = 3.5, Q3 = 11.5) and 23.5% seem to suffer from depression (Mdn = 5, Q1 = 3, Q3 = 11.5). These results are confirmed by the QLQ-C30 emotional functioning score (M = 60.78, SD = 34.58). The ACSA showed that 40% indicated that their present period was more alike their best period compared to their worst period in life (M = 0.27, SD = 3.10). NCF results are not yet available.
Klinische – maatschappelijke en/of wetenschappelijke relevantie
In view of the poor prognosis of recGB, there is an urgent need for novel treatment to improve clinical outcomes and Qol in patient’s suffering. This study investigates an innovating, experimental combination therapy which may present a valuable therapeutic approach in patients with recGB.
Impairment of NCF in patients with recGB, is very common due to the tumor itself, tumor-related epilepsy, treatment and patient-related factors (e.g. age, psychological distress). NCF has been shown to be a predictor of survival in these patients and seems to affect Qol. As neurocognitive decline often precedes radiographic evidence of tumor progression, we want to asses whether systematic NCF testing is of additional clinical and predictive value. Moreover, outcome measures evaluating Qol and emotional burden can offer additional information to judge upon the potential clinical benefits of this therapy and if found necessary, help to offer adapted psycho-social care.