[2030] Serum HER-2/neu decline predicts improved response to trastuzumab-based therapy in patients with normal and elevated baseline serum HER-2/neu levels.
Ali SM, Brault D, Brown-Shimer S, Carney W, Esteva FJ, Fornier M, Gligorov J, Hamer P, Harris L, Leitzel K, Kostler W, Lotz J-P, Luftner D, Pichon M-F, Thiel RP, Tse C, Wheler J, Lipton A.. Penn State Univ./Hershey Medical Center, Hershey, PA; Lebanon VA Medical Center, Lebanon, PA; Tenon Hospital, Paris, France; Oncogene Science/Bayer HealthCare, Cambridge, MA; MD Anderson Cancer Center, Houston, TX; Memorial Sloan Kettering Cancer Center, New York, NY; Yale Univ., New Haven, CT; Univ. Hospital of Vienna, Vienna, Austria; Humboldt Univ., Berlin, Germany; Ren
Huguenin Cancer Center, Paris, France; THIEL Stat. Consultants, New Oxford, CT; Serum HER-2/neu Study Group
Background: Trastuzumab (Herceptin) monotherapy has a 34 % objective response rate (ORR) in patients with HER-2/neu IHC 3+ or FISH-positive first-line metastatic breast cancer (C. Vogel et al, JCO 20:719-726, 2002). Predicting response and survival to trastuzumab-based therapy is an unsolved problem. The HER-2/neu extracellular domain (ECD) is released after cleavage by the ADAM metalloproteinases, and the remaining membrane-bound internal domain is constitutively activated. Trastuzumab inhibits cleavage of the HER-2/neu ECD.
Material and Methods: A pooled analysis of 7 trials of first-line trastuzumab therapy (with or without chemotherapy) with serial serum HER-2/neu levels were included. The FDA-approved HER-2/neu ELISA (Oncogene Science/Bayer HealthCare) was used to determine serum HER-2/neu levels. A pretreatment and post-treatment serum (16-120 days) from 307 patients was available. 236 patients had data on overall survival. Kaplan Meier Life table analysis was performed to compare duration of response (DRP), time to progression (TTP), and overall survival (OS).
Results: The median decrease in serum HER-2/neu levels for all patients was 31.0% (Range: 98% decrease to 239% increase). Patients with > 20% decrease in HER-2/neu levels had significantly higher ORR, and longer DRP, TTP and OS, regardless of baseline serum HER-2/neu level.
Conclusion: Patients with < 20% decrease in serum HER-2/neu levels have decreased benefit from trastuzumab therapy. Patients who do not have a significant decrease in serum HER-2/neu levels should be considered for additional HER-2/neu-targeted therapies.
| Baseline serum HER2 | HER-2/neu levels | ORR % | DRP Median (days) | TTP Median (Days) | OS Median ( Days) |
| <15ng/ml | <20% Decrease | 34 | 230 | 210 | 809 |
| <15ng/ml |  20% Decrease | 50 | 445 | 401 | Not Reached |
| <15ng/ml | p-value | 0.23 | 0.038 | 0.015 | 0.03 |
| >15ng/ml | <20% Decrease | 23.8 | 243 | 174 | 521 |
| >15ng/ml | 20% Decrease | 57.7 | 368 | 304 | 829 |
| >15ng/ml | p-value | 0.0001 | 0.134 | <0.0001 | 0.016 |
Friday, December 15, 2006 7:00 AM
Poster Session II: Prognosis and Response Prediction: Prognostic Factors I (7:00 AM-9:00 AM)