Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast
cancer.
Author(s): Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B,
Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB.
Affiliation(s): Mayo Clinic, Jacksonville, FL 32224, USA. perez.edith@mayo.edu
Publication date & source: 2011, J Clin Oncol. , 29(34):4491-7
PURPOSE: NCCTG (North Central Cancer Treatment Group) N9831 is the only
randomized phase III trial evaluating trastuzumab added sequentially or used
concurrently with chemotherapy in resected stages I to III invasive human
epidermal growth factor receptor 2-positive breast cancer.
PATIENTS AND METHODS: Patients received doxorubicin and cyclophosphamide every 3
weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A),
paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel
plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks
(arm C). The primary end point was disease-free survival (DFS).
RESULTS: Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year
median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%,
respectively. DFS was significantly increased with trastuzumab added sequentially
to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI,
0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year
median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%,
respectively. There was an increase in DFS with concurrent trastuzumab and
paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI,
0.53 to 1.11), but the P value (.02) did not cross the prespecified
O'Brien-Fleming boundary (.00116) for the interim analysis.
CONCLUSION: DFS was significantly improved with 52 weeks of trastuzumab added to
adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we
recommend that trastuzumab be incorporated into a concurrent regimen with taxane
chemotherapy as an important standard-of-care treatment alternative to a
sequential regimen.
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