Lani
11-02-2011, 02:30 AM
J Clin Oncol. 2011 Oct 31. [Epub ahead of print]
Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer.
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.
Source
Edith A. Perez and Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Vera J. Suman, Daniel W. Visscher, Beiyun Chen, James N. Ingle, Thomas M. Pisansky, and Robert B. Jenkins, Mayo Clinic, Rochester, MN; Nancy E. Davidson, University of Pittsburgh, Pittsburgh, PA; Julie R. Gralow, Seattle Cancer Center Alliance, Seattle, WA; Peter A. Kaufman, Dartmouth Hitchcock Medical Center, Hanover, NH; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; and JoAnne Zujewski, National Cancer Institute, Bethesda, MD.
Abstract
PURPOSENCCTG (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 METHODSPatients 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).ResultsComparison 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. CONCLUSIONDFS 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.
PMID: 22042958
Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer.
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.
Source
Edith A. Perez and Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Vera J. Suman, Daniel W. Visscher, Beiyun Chen, James N. Ingle, Thomas M. Pisansky, and Robert B. Jenkins, Mayo Clinic, Rochester, MN; Nancy E. Davidson, University of Pittsburgh, Pittsburgh, PA; Julie R. Gralow, Seattle Cancer Center Alliance, Seattle, WA; Peter A. Kaufman, Dartmouth Hitchcock Medical Center, Hanover, NH; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; and JoAnne Zujewski, National Cancer Institute, Bethesda, MD.
Abstract
PURPOSENCCTG (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 METHODSPatients 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).ResultsComparison 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. CONCLUSIONDFS 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.
PMID: 22042958