N0436: A phase II trial of irinotecan plus cetuximab in patients with metastatic breast cancer and prior anthracycline and/or taxane-containing therapy

Abstract

1081 Background: Irinotecan has a 23% response rate (RR) in patients (pts) with previously treated metastatic breast cancer (MBC) (Perez, JCO 2004). Epidermal growth factor receptor (EGFR) is overexpressed in MBC, especially in those with ER-/PR- and HER2-negative tumors (triple-negative, [TNeg]). Cetuximab is a monoclonal antibody against EGFR with additive activity to irinotecan in colorectal cancer with acceptable toxicity. Methods: This one-stage phase II study enrolled pts with MBC, measurable disease, and prior anthracycline and/or taxane therapy. Pts received cetuximab 400 mg/m2 day 1 cycle 1 then 250 mg/m2 weekly and irinotecan 80 mg/m2 days 1, 8 of each 21-day cycle. Primary endpoint was confirmed RR by RECIST criteria. Planned sample size was 36. Genotyping for UGT1A1 polymorphisms was performed. Results: 19 eligible pts enrolled from 2/06 to 9/06 with a median age of 49 yrs (range: 28–76), 74% had visceral disease, 32% were ER and/or PR positive, 11% were HER2 positive, 58% were TNeg. 79% had prior chemotherapy for MBC. Pts received a median of 2 cycles (range: 1–11) of treatment. Confirmed RR was 11% (95% CI: 1–33%), with 1 PR and 1 CR. One pt had stable disease for 11 cycles. RR and clinical benefit rate (CBR: RR + stable > 6 months) for Tneg vs non- Tneg was 18% vs 0% (p=0.49) and 27% vs 0% (p=0.23). 12 pts progressed on therapy within 2 cycles. With low response rate and rapid progression, the study closed early. NCI CTC version 3 grade 3–4 adverse events occurred in 10 pts; only dermatologic toxicity (derm tox) had a > 5% incidence (26%). Patients with grade ≥ 2 derm tox had a CBR of 21% (3/14) vs 0% in patients with grade 0–1. 18 pts have progressed with a median time to progression of 1.4 mos (95% CI: 1.1–2.2 mos). 15 pts have died with a median overall survival of 9.4 mos (95% CI: 3.3–16.1 mos). UGT1A1 results will be presented. Conclusions: Irinotecan and cetuximab has minimal activity in this population. Tolerability is acceptable. There was a numerically higher CBR in Tneg pts and patients with grade ≥ 2 derm tox, but small pt numbers limit conclusions. Better predictive factors for response to EGFR inhibition are needed. NCI CA-25224, CA-63848, CA-37404, CA- 60276, Bristol-Myers Squibb, Imclone systems Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb