Pseudoprogression after treatment with the TGF-beta 2 inhibitor trabedersen in high-grade glioma patients.

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2054 Background: Pseudoprogression (psPD) has frequently been described in high-grade glioma (HGG) patients after chemoradiotherapy with temozolomide (TMZ). Trabedersen (AP 12009), a TGF-beta 2 specific inhibitor, was successfully tested in three phase I/II studies and one phase IIb study in recurrent/refractory HGG. Methods: The phase IIb study was an open-label, randomized, active-controlled dose-finding study. 134 patients (pts) with recurrent/refractory anaplastic astrocytoma (WHO grade 3, AA) or glioblastoma multiforme (WHO grade 4, GBM) were treated. Main objectives were to compare response rate, survival, and safety of two doses of trabedersen vs. standard chemotherapy (TMZ/PCV). The occurrence of psPD was assessed retrospectively. Data from pre- and posttreatment central MRI assessments, clinical symptoms, steroid use, and survival were analyzed. Results: PsPD was found in 9 of 89 pts (10%) of the trabedersen group and 4 of 45 pts (9%) of the chemotherapy group. PsPD occurred in GBM and AA patients. The psPD was observed approx. 30 days after treatment start in all treatment groups. Pts with psPD had a significantly longer survival than pts without psPD (p = 0.01). The median survival in pts with psPD was 36.1 months (95%CI 18.1-ND) compared to 11.0 months (95%CI 9.0-13.2) in pts without psPD regardless of treatment. Conclusions: Our results extend previous findings of observed psPD after chemoradiotherapy. PsPD was also observed in pts treated with trabedersen, which has a completely different, immunomodulatory mechanism of antitumour activity. PsPD was associated with a prolonged survival after treatment with trabedersen. As psPD and true progression are difficult to distinguish, MRI results should be interpreted cautiously and in the context of the clinical status of the patient to avoid premature discontinuation of a possibly effective treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antisense Pharma GmbH Antisense Pharma GmbH Antisense Pharma GmbH

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