Primary malignant brain tumours (PMBT) in phase I studies: Barriers to treatment and patient outcomes.

person Scheryll Paula Alken Departments of Neuro Oncology/Drug Development, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom info_outline Scheryll Paula Alken, Karim Rihawi, Vasiliki Michalarea, Andrea Zivi, Shankar Bodla, Kathy Greenwood, Stanley B. Kaye, Udai Banerji, Johann Sebastian De Bono, Frank Saran, L Rhoda Molife

Authors person Scheryll Paula Alken Departments of Neuro Oncology/Drug Development, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom info_outline Scheryll Paula Alken, Karim Rihawi, Vasiliki Michalarea, Andrea Zivi, Shankar Bodla, Kathy Greenwood, Stanley B. Kaye, Udai Banerji, Johann Sebastian De Bono, Frank Saran, L Rhoda Molife Organizations Departments of Neuro Oncology/Drug Development, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, Drug Development Unit at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK, London, United Kingdom, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, Department of NeuroOncology, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, Drug Development Unit at The Institute of Cancer Research and The Royal Marsden Foundation Trust, London, United Kingdom, The Royal Marsden NHS Foundation Trust, Surrey, United Kingdom, Drug Development Unit at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom Abstract Disclosures Research Funding No funding sources reported Background: Primary malignant brain tumours (PMBT) are a rare tumour group with a poor outcome and limited options at relapse. Despite recent incremental gains from multimodal therapy and an emerging understanding of underlying genetic alterations, patients (pts) with PMBT have traditionally been excluded from phase I trials due to a number of concerns including blood-brain barrier penetration; it is recognised that such concerns are less relevant in the molecular era. We examined the outcomes of and barriers to participation of these pts on phase I studies. Methods: We reviewed the case records of pts with PMBT referred to the Neuro Oncology and Clinical Pharmacology Units of the Royal Marsden Hospital between 2004 and 2013 for consideration of a phase I study. Pt characteristics including demographics and details of prior treatment were examined. Kaplan-Meier estimator and Cox regression were used to evaluate progression free survival (PFS) and overall survival (OS). All tests performed were two-sided with an alpha of 0.05, and a power of 80% was used. Surviving patients were censored at date of last follow-up. Results: Seventy three pts with PMBT were identified. Of these, 50 (68.5%) were allocated to a phase I trial and 38 (52%) of these patients received at least one dose of the study drug. 9 pts (18%) failed screening, 3 pts (6%) withdrew consent. 11 pts (15%) were not allocated to a study due to a lack of suitable trials, 9 (12%) were not allocated due to poor performance status (PS). Factors influencing enrolment were examined; only Karnofsky PS (KPS) was statistically significant (HR 1.09, 95% CI 1.04 – 1.15, p=0.001). The median PFS of pts dosed was 7.3 months. The median OS of these pts was 7.9 months versus 4.2 months in those not dosed (p=0.024). Grade 3 drug related toxicities were seen in 9.6% of patients. Conclusions: Patients with PMBT can be safely treated in phase I trials. A lack of suitable trials remains the main barrier to enrolment, as does KPS, which is similar to other rare malignancies. Based on our results these patients tolerate investigational agents similar to other groups. This study adds to the growing body of evidence encouraging investigators to enrol such patients.