[3042] Updated efficacy and safety analyses of 3-weekly Herceptin monotherapy in women with HER2-positive metastatic breast cancer: results from twelve months of follow-up to a phase II study.
Baselga J, Carbonell X, Castaneda-Soto N-J, Clemens M, Green M, Harvey V, Morales S, Barton C.. Hospital Val D
Hebron, Barcelona, Spain; Instituto Nacional de Cancerolog
a, Tlalpan, Mexico; Mutterhaus der Borromaeerinnen, Trier, Germany; Royal Melbourne Hospital, Melbourne, Australia; Auckland Hospital, Auckland, New Zealand; Hospital Arnau de Vilanova, Lleida, Spain; Roche Products Ltd, Welwyn Garden City, United Kingdom
Background: Standard weekly dosing of trastuzumab (H; Herceptin) is well tolerated and efficacious, but less frequent dosing would be more convenient for patients. A 3-weekly (q3w) schedule was shown to have similar exposure, efficacy and safety as the standard weekly regimen in the main analysis of study WO16229, a phase II study of pharmacokinetics, efficacy, and safety of a q3w regimen of H monotherapy in patients (pts) with HER2-positive metastatic breast cancer (MBC). Results of an updated analysis of efficacy and safety performed after 12-months of additional follow-up (30 months after the last pt entered) are reported.
Methods: 105 pts with previously untreated HER2-positive (IHC 3+ and/or FISH positive) MBC were enrolled. Treatment: H 8mg/kg i.v. loading dose, followed by 6mg/kg q3w until progression.
Results: At the main analysis (18 months after the last pt entered) 11 pts (10%) continued to receive H. 1 pt was lost to follow-up; 10 pts continued H therapy in the follow-up period. Duration of treatment: 8 pts received H for more than 30 cycles (23 months); 5 of these pts received more than 40 cycles (30 months) and, of these, 1 received more than 50 cycles (>37 months) of treatment. 5 pts discontinued treatment in follow-up; 4 withdrew due to progressive disease and 1 pt withdrew to start chemotherapy (paclitaxel); 5 pts continue to receive H. Updated efficacy analysis (30 months after the last pt entered): overall response rate (ORR) in the intent-to-treat population was 20% (3 CR, 18 PR) and the overall clinical benefit rate (CBR) was 33%. In pts with measurable disease and HER2 positivity confirmed by central testing ORR was 24% and CBR was 36%. Median time to response in all evaluable pts was 1.4 (1
20) months and the duration of response was 10.1 (2.8
35.6) months. Extended exposure to H was well tolerated with no serious adverse events (AEs) or AEs leading to death or discontinuation of treatment reported in the follow-up period. 6 patients reported a total of 19 adverse events in the follow-up period; all were mild (14 events) to moderate (5 events) in severity. In the 5 pts who continued to receive H
, only 1 pt had a temporary drop in LVEF >15% from baseline (by 16% points; day 286). No other pt had any major LVEF changes during at least 22 months of treatment or developed symptomatic cardiac failure.
Conclusion: Long-term administration of H (>30 months) q3w is a well-tolerated alternative dosing regimen. These data demonstrate the effectiveness and overall feasibility of the q3w schedule.
Thursday, December 9, 2004 4:30 PM
Poster Session: Treatment: Antibody-based Regimens (4:30 PM-6:30 PM)
Regards
Joe