Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG).

BACKGROUND: Sequential administration of anthracycline and taxane is the current standard of care adjuvant regimen for node-positive early breast cancer. Due to long-term toxicity concerns, anthracycline-free regimens have been developed. We compared a sequential dose-dense anthracycline and taxane regimen with the anthracycline-free regimen of docetaxel and cyclophosphamide. PATIENTS AND METHODS: In this randomized, non-inferiority, phase III trial, women with HER2-negative invasive breast cancer and at least one positive axillary lymph node were randomized to receive either epirubicin (75 mg/m(2)), 5-fluorouracil (500 mg/m(2)) and cyclophosphamide (500 mg/m(2)) every 2 weeks for four cycles, followed by four cycles of docetaxel (75 mg/m(2)) every 2 weeks with prophylactic G-CSF support (FEC → D) or docetaxel (75 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 21 days for six cycles (TC). The primary end point of the study was the 3-year disease-free survival (DFS) rate. RESULTS: Six hundred and fifty women were randomized to either FEC → D (n = 326) or TC (n = 324). After a median follow-up of 46 and 47 months, the 3-year DFS rate was 89.5% and 91.1% for the FEC → D and TC arm, respectively (hazard ratio = 1.147, 95% confidence interval 0.716-1.839, P = 0.568). Grade 3-4 neutropenia was higher in the TC arm (32.4% versus 10.5%, P = 0.0001). The incidence of neutropenic fever was low (<1%). Nausea, vomiting, hand-foot syndrome and fatigue (grade 3-4) were more common with FEC → D. Acute cardiotoxicity was rare (1 event in each group). There were no toxic deaths. CONCLUSIONS: This trial did not clearly demonstrate that TC is non-inferior to dose-dense FEC → D. However, 3-year DFS rates were excellent in both arms for women with node-positive, HER2-negative early breast cancer. CLINICALTRIALSGOV: NCT01985724.

Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG).

BACKGROUND: Adjuvant trastuzumab in combination with chemotherapy improves survival of women with HER2-positive early breast cancer. In this study, we compared 12 versus 6 months of adjuvant trastuzumab. PATIENTS AND METHODS: Axillary node-positive or high-risk node-negative women with HER2-positive early breast cancer were randomized to receive 12 or 6 months of adjuvant trastuzumab concurrently with dose-dense, granulocyte colony-stimulating factor (G-CSF)-supported docetaxel (75 mg/m(2) every 14 days for four cycles). All patients received upfront dose-dense, G-CSF-supported FEC (5-fluorouracil 700 mg/m(2), epirubicin 75 mg/m(2), cyclophosphamide 700 mg/m(2) every 14 days for four cycles). Randomization was carried out before commence of chemotherapy. The primary end point was the 3-year disease-free survival (DFS). RESULTS: A total of 481 patients were randomized to receive 12 months (n = 241) or 6 months (n = 240) of adjuvant trastuzumab. Chemotherapy was completed in 99% and 98% of patients, while trastuzumab therapy in 100% and 96% of patients in the 12- and 6-month groups, respectively. After 47 and 51 months of median follow-up, there were 17 (7.1%) and 28 (11.7%) disease relapses in the 12- and 6-month groups (P = 0.08). The 3-year DFS was 95.7% versus 93.3% in favor of the 12-month treatment group (hazard ratio = 1.57; 95% confidence interval 0.86-2.10; P = 0.137). There was no difference in terms of overall survival and cardiac toxicity between the two groups. CONCLUSIONS: Our study failed to show noninferiority for the 6-month arm. The results further support the current standard of care that is administration of adjuvant trastuzumab for 12 months.

Randomized phase III trial comparing docetaxel plus epirubicin versus docetaxel plus capecitabine as first-line treatment in women with advanced breast cancer.

BACKGROUND: The purpose of this study was to compare docetaxel plus epirubicin versus docetaxel plus capecitabine combinations as front-line treatment in women with advanced breast cancer (ABC). PATIENTS AND METHODS: Previously untreated patients with ABC were randomly assigned to receive docetaxel 75 mg/m(2) plus epirubicin 75 mg/m(2) (DE) on day 1 or docetaxel 75 mg/m(2) on day 1 plus capecitabine 950 mg/m(2) orally twice daily on days 1-14 (DC) in 21-day cycles. Previous anthracycline-based (neo)-adjuvant chemotherapy was allowed if completed >1 year before enrollment. The primary objective of the study was to compare time to disease progression (TTP). RESULTS: One hundred and thirty-six women were treated on each arm and median TTP was 10.6 versus 11.0 months (P = 0.7), for DE and DC, respectively. According to RECIST criteria we observed 15 (11%) versus 11 (8%) complete responses and 55 (40%) versus 61 (45%) partial responses (P = 0.8), with DE and DC, respectively. Severe toxicity included grade 3-4 neutropenia (57% versus 46%; P = 0.07), febrile neutropenia (11% versus 8%; P = 0.4), hand-foot syndrome (0% versus 4%; P = 0.02), grade 2-3 anemia (20% versus 7%; P = 0.001) and asthenia (12% versus 6%; P = 0.09) with DE and DC, respectively. CONCLUSIONS: The DE and DC regimens have similar efficacy but different toxicity. Either regimen can be used as front-line treatment of ABC.