Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 1507
© 2005 American Society of Clinical Oncology

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Abstract

Phase II study of erlotinib in recurrent GBM: Molecular predictors of outcome

UCLA, Los Angeles, CA; M.D. Anderson, Houston, TX; Duke, Durham, NC; M.D. Anderson Cancer Ctr, Houston, TX; Genentech, San Francisco, CA; UCSF, San Francisco, CA

1507

Background: Erlotinib (Tarceva) is an orally active, highly potent and selective inhibitor of the epidermal growth factor receptor (EGFR). Preliminary results from this phase II trial of erlotinib for GBM in first relapse have been reported (ASCO 2004, Abs#1555). Updated clinical results and molecular characterization of archival tissue samples are now available. Methods: A multi-institutional phase II clinical trial of single agent erlotinib until disease progression enrolled GBM patients with measurable disease in first relapse. Individual dose titration until dose-limiting toxicity (diarrhea, rash, other) was allowed in 2 dose cohorts: patients taking enzyme-inducing anti-epileptic drugs or not. Subjects were evaluated for response every 8 weeks. Submission of archival tissue was mandatory. Depending on the amount of tissue available, the following assays were performed: EGFR amplification by FISH (Vysis); and EGFR, EGFRvIII (Zymed) and PTEN expression by IHC. Results: Forty-eight subjects (19 female, 29 male) with a median age of 51 years (37–73) were enrolled over 3 months from 4 centers. The investigator determined response rate (WHO criteria) was 8.4% (3 PR, 1CR), with SD as the best response in 37.5% (n=18). One SD patient who died of an MI at day 84 had only microscopic foci of viable tumor amidst significant necrosis on autopsy. The 6 month PFS rate was 17% and median survival was 10 months. Tissue is missing from 1 PR with the longest ongoing response. EGFRvIII analysis is ongoing. Conclusions: Erlotinib is active in recurrent GBM, with a promising response rate, 6 m PFS and median survival. Molecular analyses show a slight trend towards better outcome with EGFR expression however, the differences are not significant due to the small numbers.

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Abstract presentation from the 2005 ASCO Annual Meeting