Phase II trial to study the efficacy and toxicity of combined docetaxel (D), carboplatin (C), +/- trastuzumab (T) administered weekly (W) in patients (pts) with HER2/neu +/- metastatic breast cancer (MBC)

Abstract

832 Background: D as a single agent is associated with the highest reported response rates (RR) and response duration in MBC. Though D is commonly delivered a q 3 week dose, newer studies have shown that W delivery of the drug is safe and associated with an equal or greater RR and less toxicity. C is an active agent in MBC and has shown synergy with the taxanes. Synergism has been established between the taxanes, C and T. The use of D+C on a q3 week basis +/- WT in HER2neu +/- MBC has been shown to have very high RR. As it appears that W administration of a combination of Paclitaxel (P), C and T results in higher RR and less toxicity than q 3 week P + C with WT in HER2neu+ pts, the question is whether this is also true with D based regimens. Methods: We are studying the safety and efficacy of WD at 25mg/m2 iv and WC at AUC 2 iv, given days 1, 8, 15 q 28 days, with WT given iv only for FISH + HER2neu pts with a loading dose of 4mg/kg on week 1 and then 2mg/kg/week in previously untreated women with MBC. All pts receive 10mg dexamethasone pre-medication intravenously one hour before D administration. The objectives of the study are to evaluate RR, safety, and time to progression (TTP). All pts are restaged q 8 weeks. Results: We have to date enrolled 23 pts. Of the 20 evaluable pts, there is 1 CR, 3PR, 9SD, 7PD, yielding a 65% clinical benefit (CR, PR, SD) and a 20% RR. Of the 7 evaluable HER2neu+ pts on the DCT regimen, there are 3 PR, 2SD and 2PD, yielding a 43% RR and a median TTP of 217 days. Of the 13 evaluable pts on DC alone there are 7SD, 1CR, and 5PD, yielding a 62%CB, but only an 8% RR with a median TTP of 118 days. Toxicity: The regimen was well tolerated with no significant toxicity. Conclusions: Though q 3 week DC+/-T is established as highly active for MBC, the efficacy of WDC+/-T needs further testing. Clearly this is a safe and tolerable regimen, and it may be that the efficacy of the WDC is best seen in the HER2neu+ patients when T is also administered. Enrollment continues and updated data will be presented. A trial of q 3 week DC+/-T vs WDC+/-T is warranted to assess the best way to use DC in MBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb