Phase II study of weekly administration of docetaxel (D) in combination with the epidermal growth factor receptor (EGFR) inhibitor erlotinib (E) in metastatic breast cancer (MBC).

Abstract

Abstract Abstract #3124 Background: Single agent weekly docetaxel (D) is an active agent in the treatment of metastatic breast cancer (MBC) with response rates of 29% - 53%. Erlotinib (OSI-774, Tarceva®) is a tyrosine kinase inhibitor directed against EGFR, which is overexpressed in 30-40% of breast cancers, making EGFR an attractive treatment target. This study was designed to assess the combination of D and E in previously untreated recurrent and/or MBC.
 Methods: Adult patients with histologically confirmed MBC without prior chemotherapy for recurrence or metastases were eligible. Treatment plan was: D (initially 35 mg/m2 intravenous infusion weekly x 3 every 4 weeks) and E 150 mg orally daily uninterrupted. In patients with responding or stable disease, E was continued in 4 week cycles following a minimum of 6 cycles of D and E. Estimates of overall survival (OS) and progression free survival (PFS) were made by Kaplan-Meier method and the difference between groups by log-rank test. Tumor EGFR expression by immunohistochemisty and ER/PR was correlated with OS and PFS.
 Results: 39 female pts were enrolled between 12/02 and 8/06. The median age was 51 yrs (range 28-78). The median number of cycles of D and E received was 4 (range 1-26) and of E following D and E was 11 (range 2-18). EGFR, ER/PR and Her-2/neu status was determined on 35/39 patients. EGFR: 23 positive, 12 negative. ER/PR: 25 positive, 10 negative. Her-2/neu: 2 positive, 33 negative. Ten pts. were not evaluable for survival or response due to toxicity occurring within the first cycle. Best responses (n=29) ; PR 11(39%), SD 4 (14%), PD 13 (45%), and clinical benefit (PR+SD) 15 (54%). Median PFS was 8 mos (95% CI: 4.4-12.2). PFS for EGFR negative tumors appeared better than EGFR positive tumors (12 mos PFS 33% vs. 23%) but was not significant (p = 0.53). There was no difference in OS between these groups (p=0.38). PFS and OS for ER/PR positive pts was significantly higher than ER/PR negative pts 6 mos PFS 67% vs. 25% (p= 0.009) and 2 yr OS 53.9% vs. 12.5% (p=0.015). , All patients were included for toxicity assessment (n-39). The first 26 pts received planned D dose of 35mg/m2. Because of non-hematologic toxicity, trial was subsequently modified to start D at 25 mg/m2. Grade 3 or 4 Leukopenia was seen in 15% pts. Principal non-hematologic grade 3-4 toxicities included anorexia, diarrhea, and fatigue (18% pts).
 Conclusions: Combination therapy for advanced breast cancer with docetaxel and erlotinib shows promising activity with favorable response compared with other studies. There was no significant association with EGFR expression and PFS, however this combination is more favorable for ER positive patients. Randomized trials for ER positive disease is warranted to further investigate the efficacy of this combination compared to single agent docetaxel. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3124.