A phase II trial of trastuzumab (H) + capecitabine (X) as first-line treatment in patients (pts) with HER2-positive metastatic breast cancer (MBC)

Abstract

10615 Background: The addition of H to a taxane provides significant clinical benefit, including prolonged survival, in HER2-positive MBC. H adds little to the toxicity of taxanes alone. As monotherapy, X has consistently high activity and favorable safety. The addition of X to docetaxel extends survival in MBC. Preliminary data [Bangemann et al. 2000] indicated that the combination of H + X is effective and well-tolerated for intensively pretreated HER2-positive MBC (ORR 47%). The current study evaluated the efficacy and safety of H + X in first-line MBC. Methods: 72 pts of a planned population of 100 pts were enrolled between Mar03 and Dec05. All pts had measurable (WHO criteria), HER2-positive (IHC 3+ or IHC 2+/FISH positive) and untreated MBC, KPS ≥60, and adequate organ function. H was administered as a 4mg/kg loading dose followed by 2mg/kg i.v. weekly (until disease progression) and X 1250mg/m2 bid d1–14 q3w (max 6 cycles). The primary endpoint was progression-free survival (PFS). Results: Baseline characteristics: median age 49 years (range 27–74), median KPS 90 (range 60–100). Principal tumor sites: lymph nodes (49%), lung (33%), liver (28%), breast (14%), thoracic wall (9%), chest (9%), other (12%). Prior treatment: surgery (77%), radiotherapy (21%), and adjuvant chemotherapy (58%), including anthracycline (35%), paclitaxel (7%), docetaxel (7%) and other (21%). 43 pts are evaluable for safety and efficacy. The remaining 29 pts are being analyzed. 6 pts received 3 cycles of H + X; the other 37 pts completed 6 cycles of treatment. 16 pts received H monotherapy after completing 6 cycles of H + X. 3 pts discontinued H due to disease progression. The most common grade 1/2 adverse events (AEs) were HFS (14%), neutropenia (14%), SGOT abnormality (16%), and SGPT abnormality (14%). Grade 3 HFS occurred in 4 pts (10%) with grade 3 myelosuppression in 1 pt (2%). AEs were mild and resolved in all pts. The overall response rate was 63%, including 5 CRs and 22 PRs. At a median follow-up of 6 months, median PFS has not been reached. Conclusions: The combination of H and X is a highly active and well-tolerated regimen for first-line treatment of HER2-positive MBC. Updated data will be presented. No significant financial relationships to disclose.

Phase II Study of Bevacizumab in Combination with Trastuzumab and Capecitabine as First-Line Treatment for HER-2-positive Locally Recurrent or Metastatic Breast Cancer

“…Diarrhea, HFS, and nausea were the most common AEs across both treatment groups. The high clinical activity of trastuzumab plus capecitabine combination therapy was also reported in three singlearm, phase II studies as first-line (n ϭ 63) and later lines of treatment (n ϭ 74) in HER-2-positive MBC patients [16,17,28]. In the first-line setting, ORRs were Ͼ60%, with a median TTP of 9.2 months and median OS time of 25.6 months [16,17].…”

“…The high clinical activity of trastuzumab plus capecitabine combination therapy was also reported in three singlearm, phase II studies as first-line (n ϭ 63) and later lines of treatment (n ϭ 74) in HER-2-positive MBC patients [16,17,28]. In the first-line setting, ORRs were Ͼ60%, with a median TTP of 9.2 months and median OS time of 25.6 months [16,17]. A number of clinical trials have demonstrated the efficacy of doublet combinations of trastuzumab, bevacizumab, and capecitabine in patients with MBC [11,[15][16][17].…”

The Role of Capecitabine in First-Line Treatment for Patients with Metastatic Breast Cancer

“…In the firstline setting, the overall response rate was 73%, including a 15% complete response rate. An additional eight patients (20%) had stable disease, leading to a clinical benefit in 93% of patients [3]. The only grade 3 adverse events were hand-foot syndrome in four patients and leukopenia in one patient, but both resolved with dose interruption or reduction.…”

“…Capecitabine-based therapy has also been evaluated in HER-2-positive MBC, and the first phase III trial will report in 2006. Capecitabine plus trastuzumab has shown high first-line activity [3] and is also highly active in patients with pretreated disease [63,64]. In the firstline setting, the overall response rate was 73%, including a 15% complete response rate.…”

“…In the premenopausal setting, treatment may include tamoxifen, alone or together with ovarian suppression, and in the postmenopausal setting, an aromatase inhibitor (such as anastrozole, letrozole, or exemestane) or fulvestrant. Trastuzumab (Herceptin ® ; F. Hoffmann-La Roche, Basel, Switzerland) has been studied as a single agent and in combination with several chemotherapies and has shown a survival benefit in patients with human epidermal growth factor receptor 2 (HER-2)-positive disease [1][2][3][4], making it an optimal standard of care for HER-2-positive breast cancer. Initial data on combined trastuzumab and anastrozole in advanced breast cancer appear promising [5].…”