HOUSTON-"Interesting antitumor activity" was seen in the first stage of a phase II trial of erlotinib (Tarceva) for glioblastoma multiforme in first relapse, according to W.K. Alfred Yung, MD, of The University of Texas M.D. Anderson Cancer Center, Houston (abstract 1555). There appeared to be a slightly higher response rate in patients whose tumors overexpressed the epithelial growth factor receptor (EGFR) by fluorescence in situ hybridization (FISH+), but response was not limited to those patients, he reported. "FISH-negative patients should not be excluded from future studies until this relationship is studied more carefully," Dr. Yung said. Erlotinib has documented clinical activity in glioblastoma multiforme, and Dr. Yung noted that this tumor is an interesting target for EGFR inhibitors because it typically has a high rate of EGFR gene amplification and of activating mutations in EGFR, such as EGFRvIII. Dr. Yung reported a multi-institutional phase II clinical trial of the single agent erlotinib that was initiated in August 2003 for glioblastoma multiforme patients with measurable disease in first relapse. Higher Starting Dose "Erlotinib is metabolized by CYP3A4. Therefore, to ensure adequate exposure, patients receiving enzyme-inducing antiepileptic drugs (EIAED group) receive a higher starting dose (300 mg/d). Otherwise, the standard dose of 150 mg/d was given (non-EIAED group)," Dr. Yung said. Individual dose titration until dose- limiting toxicity (diarrhea, rash, other) was allowed. This ranged from 150 to 200 mg in the non-EIAED group and from 300 to 500 mg in the EIAED group. The primary study objectives were to estimate the objective response rates in glioblastoma multiforme patients, irrespective of tumor EGFR amplification and with tumors positive for HER1/EGFR amplification. An additional objective was investigating the safety and tolerability of single-agent erlotinib. The study had a two-stage enrollment that was based on the number of responses in the first 47 patients and whether responses occurred in patients with or without HER1/EGFR gene amplification. Radiography was repeated every 8 weeks, and responding patients had confirmatory scans at 4 weeks and review by an independent radiologic facility. Rash, Diarrhea Most Common Forty-eight subjects were enrolled (19 female, 29 male), with a median age of 50 years (range 37-70). One patient did not receive the study drug, so Dr. Yung reported data on 47 patients. Of these, 20 were on EIAED and 27 were not. In the EIAED group, 10 (50%) were FISH-positive. In the no-EIAED group, 13 (54%) were FISH-positive. All had previous radiation therapy, and 75% had one previous chemotherapy regimen. Median follow-up was 6.25 months. Dr. Yung reported that 57% of patients had grade 3 or higher adverse events, most commonly rash (19%) and diarrhea (4%). One patient discontinued therapy due to grade 3 rash. Forty-five patients were evaluable for response. "Three patients responded: two partial responses (PR), one complete response (CR)," Dr. Yung said. The complete responder, however, did not have the required level of measurable disease at entry (> 1 cm tumor), and independent radiology review confirmed only one of the two partial responses. "The patient remains on study at month 7 with an ongoing PR based on an investigator-determined response," Dr. Yung said. Gene amplification, as determined by FISH, has been seen in 16 of 30 subjects tested. Clinical benefit (CR, PR, or stable disease) was observed in 57% of patients with high HER1/EGFR expression and in 35% of FISHnegative patients. "Additional analyses will investigate the relationship between response and molecular correlates. Ongoing work will explore whether EGFRvIII alone or in combination with FISH status improves the ability to predict response to erlotinib," Dr. Yung told Oncology News International.