Etirinotecan pegol (EP, NKTR-102) in the treatment of high-grade glioma (HGG): A phase 2 trial.
Central Nervous System Tumors
Central Nervous System Tumors
2014 ASCO Annual Meeting
J Clin Oncol 32:5s, 2014 (suppl; abstr 2096)
2014 ASCO Annual Meeting!
Session: Central Nervous System Tumors
Type: General Poster Session
Time: Saturday May 31, 1:15 PM to 5:00 PM
Location: S Hall A2
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Author(s): Seema Nagpal, Cathy Kahn Recht, Urooj Imtiaz, Sophie Bertrand, Reena Parada Thomas, Abdulrazag Ajlan, Justine Pena, Megan Gershon, Pamela L. Kunz, Gordon Li, Lawrence David Recht; Stanford Cancer Institute, Stanford, CA; Stanford University School of Medicine, Stanford, CA
Background: Patients with recurrence of HGG after bevacizumab (BEV) have an extremely poor prognosis and generally do not respond to further treatment. EP is the first long-acting topoisomerase-I inhibitor designed to concentrate in and provide continuous tumor exposure throughout the entire chemotherapy cycle. Becasue irinotecan has demonstrated activity against HGG, we conducted a Phase 2, single arm, open label trial to evaluate EP in HGG patients who progressed after BEV. Methods: Patients age >18 with histologically proven anaplastic astrocytoma (AA) or glioblastoma (GB) who previously received standard chemo-radiation and recurred after BEV were eligible. A predicted life expectancy > 6 weeks, KPS ≥ 50 and adequate organ and bone marrow functions were required for entry. Primary endpoint was PFS at 6-week, secondary endpoints were survival from first EP infusion, overall survival from date of pathologic diagnosis of HGG, and safety profile of EP. Response was assessed by RANO criteria. EP as a single agent is administered IV every 3 weeks at 145mg/m2. Patients did not receive BEV while on EP. Results: Between August 2012-May 2013, 20 patients were enrolled. Median age was 50 years, median KPS was 70%. 90% of patients had GB with a median time of 1 year from a diagnosis of HGG to study entry with a median of 3 prior lines of therapy. Patients received a median of 3 cycles (1-19) of EP. All patients were evaluable for PFS and toxicity. 2 patients (both with GB) had partial MRI responses. 10 patients had stable disease. 2 patients are still on treatment after receiving 19 and 9 treatment cycles. 6-week PFS was 55%. Median and 6-month PFS were 1.9 mos and 10%, respectively. Median overall survival from first EP infusion was 4.1 months. Only one patient (5%) had a Grade 3 toxicity (diarrhea with dehydration) attributable to EP. Hematologic toxicity was mild. Conclusions: Despite discontinuing BEV prior to starting EP, 2 patients had confirmed partial responses (10%) according to RANO criteria and an additional six patients had stable disease at their 1st and 2nd imaging assessment. These encouraging clinical data combined with a favorable safety profile warrant further clinical investigation of this agent in GB. Clinical trial information: NCT01663012.
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