Remarkable complete pathologic response rate after preoperative paclitaxel, gemcitabine, and trastuzumab chemotherapy in HER2 positive stage II/III breast cancer: a phase II multicenter study.

Abstract

Abstract Abstract #5105 Background: Preoperative paclitaxel (P) and gemcitabine (G) combination therapy given on D1/D8 every 3 weeks (wks) for 4 cycles was well tolerated and effective in stage II/III breast cancer (BC) in our previous phase II study, with an 18% pathological complete response (pCR) rate. Adding trastuzumab (H) to the preoperative chemotherapy increases both of the clinical and pathological response rates in HER2 positive BC patients (pts). Thus far, the highest pCR rate reported in the literature was obtained with anthracycline-based regimens in combination with trastuzumab. This study evaluated whether non-anthracycline combination chemotherapy with PGH could improve the pCR rate in HER2 positive BC. Methods: HER2 positive, stage II/III BC pts with cytologically confirmed axillary lymph node (LN), ≥ 18 years of age, with adequate organ function, and good performance status were eligible. No prior therapy was allowed. Pts received H intravenously (iv) at 4 mg/kg on D1 of the first cycle with subsequent weekly doses of 2 mg/kg in combination with P 80 mg/m2 and G 1,200 mg/m2, iv, on D1/D8 every 3 wks for 6 cycles. Within 2 wks postoperatively, patients received H 6 mg/kg every 3 wks for 11 cycles with tamoxifen or an aromatase inhibitor for 5 years if indicated. All pts received postoperative radiation therapy. Initial evaluation included sonogram and MRI of the breast, MUGA scan, or echocardiogram, and PET-CT. Results: All 53 planned pts were enrolled between April 2007 and February 2008. The median age was 43 years (range, 26–61 years), the median primary tumor size by sonogram was 5.3 cm (range, 2.0 to > 12 cm) with 89 % ≥ stage IIIA, 42% T3/T4, and 28% N3. Twenty four tumors (45%) were multiple and 20 tumors (38%) were ER positive. By May 2008, 47 patients completed surgery with a 74% breast conservation rate. Twenty-eight of 47 (60%; 95% CI, 45-72) patients achieved pCR in both the tumor and lymph node, with 68% (32/47; 95% CI, 54-80) pCR in the primary tumor, and 77% (36/47; 95% CI, 63-86) pCR in the axillary LN. Median metastatic focus in 21 positive LNs (n=11 pts) was 1 mm (range, <1–13mm). Grade III/IV adverse events (AE) were neutropenia (53%), febrile neutropenia (4%), and transient elevation of AST/ALT (9%). After 6 cycles of PGH chemotherapy, all patients maintained above normal LVEF. Conclusions: A remarkably high pCR was obtained by non-anthracyline based PGH combination therapy for HER2 positive stage II/III breast cancer. This combination is well tolerated with mild degree of AEs.
 Supported by NCC Grant No 0610240-3. Trastuzumab, paclitaxel, and gemcitabine were supplied by Roche, CJ Cheiljedang CO., and Eli Lilly and CO., respectively. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5105.