Docetaxel and Herceptin Both Show Benefit in FinHer Trial

SAN ANTONIO—Nine weeks of trastuzumab (Herceptin) given concurrently with single-agent docetaxel (Taxotere) or vinorelbine (Navelbine) prior to combination chemotherapy improves survival in HER2-positive breast cancer patients, compared with no trastuzumab, with the docetaxel regimen having a slight advantage over vinorelbine. Heikki Joensuu, MD, of Helsinki University Central Hospital, reported the results of the adjuvant therapy trial at the 28th Annual San Antonio Breast Cancer Symposium (abstract 2).

The FinHer Trial tested the hypothesis that brief use of trastuzumab, given together with potentially synergistic chemotherapy, may be more effective as adjuvant treatment for HER2-positive breast cancer than chemotherapy alone.

The interim analysis, with a median follow-up of 3 years, included 1,010 patients randomized from 17 centers in Finland, including 232 (23%) with HER2 amplification. Patients had node-positive breast cancer or node-negative tumors that were greater than 2 cm and progesterone-receptor negative.

All participants received docetaxel 100 mg/m2 (amended to 80 mg/m2 in 59% of patients to decrease febrile neutropenia) for three 3-week cycles or eight weekly cycles of vinorelbine 25 mg/m2, as adjuvant therapy. Single-agent docetaxel/vinorelbine was followed in both arms by three 3-week cycles of FEC (fluorouracil 600 mg/m2, epirubicin 60 mg/m2, and cyclophosphamide 600 mg/m2), with tamoxifen given for 5 years for hormone-positive disease.

Patients whose tumor showed HER2 amplification by chromogen in situ hybridization (CISH) analysis had a second randomization to receive nine weekly cycles of trastuzumab 2 mg/kg, concomitantly with either of the single agents, or no trastuzumab.

Fewer Recurrences With Docetaxel

Breast cancer recurrence (distant or locoregional, or contralateral breast cancer) was significantly less frequent among patients treated with docetaxel/FEC than among those treated with vinorelbine/FEC. Recurrence-free survival was 91.3% with docetaxel/FEC and 86.4% with vinorelbine/FEC, for a hazard ratio of 0.58 favoring docetaxel (P = .005). Overall survival was similar for the arms, at 96.4% and 95.5%, respectively, Dr. Joensuu said.

Docetaxel was associated with more adverse events than vinorelbine, especially grade 3-4 neutropenia (98% vs 58%) and neutropenic fever (24% vs 3%). When the docetaxel dose was reduced to 80 mg/m2, the febrile neutropenia rate decreased from 37% to 15%, he said. Grade 3-4 toxicity of any type was observed in 100% of docetaxel recipients vs 81% of patients in the vinorelbine arm.

Benefit of Trastuzumab

Trastuzumab (in the combined trastuzumab-containing arms) conferred significant benefit for recurrence-free survival and a trend toward benefit in overall survival. Recurrence-free survival was 89.3% for all patients receiving trastuzumab, compared with 77.6% in the control arm, for a risk reduction of 58% (P = .01). Overall survival was 96.3% and 89.7%, respectively (P = .07).

Trastuzumab given with either docetaxel or vinorelbine was well tolerated and did not increase toxicity above that seen with the single agents. Left ventricular ejection fraction (LVEF) was maintained in patients with HER2-positive disease, Dr. Joensuu said. LVEF decreased by greater than 15% from baseline in 3% of the trastuzumab group and 6% of controls. Cardiac failure was observed in 0% and 1%, respectively. "This makes monitoring of LVEFs unnecessary for most patients," he said.

The investigators concluded that adjuvant docetaxel improves recurrence-free survival, compared with vinorelbine, but at the expense of increased adverse events.

"Also," Dr. Joensuu said, "the brief use of adjuvant trastuzumab administered concomitantly with docetaxel or vinorelbine is well tolerated and effective, and requires few patient visits and limited costs as a treatment. A randomized comparison of the brief and 1-year regimens appears warranted."