TY - JOUR
T1 - Impact of adjuvant trastuzumab on locoregional failure rates in a randomized clinical trial
T2 - North Central Cancer Treatment Group N9831 (alliance) study
AU - Vargas, Carlos E.
AU - Thorpe, Cameron S.
AU - Dueck, Amylou C.
AU - Tenner, Kathleen S.
AU - Davidson, Nancy E.
AU - Martino, Silvana
AU - Pisansky, Thomas M.
AU - Hwang, E. Shelley
AU - Halyard, Michele Y.
AU - Pockaj, Barbara A.
AU - Perez, Edith A.
N1 - Funding Information:
Silvana Martino has received grants from Southwest Oncology Group and has received personal fees from Merck, GSK, Morpho Sys, Eli Lilly, Steba, Celltrion, Daichii Sankyo, Karyopharm, and Puma. The other authors made no disclosures.
Funding Information:
This study was supported by the National Cancer Institute of the National Institutes of Health under award numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA233196, UG1CA233328, U10CA180820 (ECOG‐ACRIN), and U10CA180888 (SWOG) and was also supported in part by funds from Genentech. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 American Cancer Society
PY - 2020/12/15
Y1 - 2020/12/15
N2 - Background: The goal of this study was to assess the impact of trastuzumab on locoregional failure. METHODS: The analysis included 2763 patients with HER2-positive (HER2+) breast cancer who were randomly assigned to adjuvant doxorubicin (A), cyclophosphamide (C), paclitaxel (T) and trastuzumab (H) (arm A, AC→T [n = 922]; arm B, AC→T→H [n = 988]; arm C, AC→T+H→H [n = 853]). Radiotherapy was given after AC→T concurrently with H. Radiotherapy was given after lumpectomy (L) or after mastectomy (M) with ≥4 positive lymph nodes but was optional for 1 to 3 positive lymph nodes. Locoregional failures at 10 years (LFR10) as first events were compared using competing risk analysis. Results: The median follow-up was 13.0 years. The first site of failure was local-only in 96 cases, locoregional in 16 cases, regional in 32 cases, and not specified in 2 cases; LFR10 was 4.8% (95% CI 4.1%-5.7%). LFR10 was 5.5% (95% CI 4.3%-7.2%), 4.9% (95% CI 3.7%-6.4%), and 2.8% (95% CI 1.9%-4.1%) in arms A, B, and C (B vs A: hazard ratio [HR] 0.91, P =.62; C vs A: HR 0.72, P =.12). For estrogen receptor–positive patients, LFR10 was 3.7% (95% CI 2.8%-4.8%) and for estrogen receptor–negative patients, it was 6.1% (95% CI 5.0%-7.4%; HR 0.61, P =.004). Local treatment included L+RT (n = 1044 [38%]), M+RT (n = 1025 [37%]), and M (n = 694 [25%]). LFR10 was 6.% (95% CI 5.0%-7.8%), 3.0% (95% CI 2.1%-4.3%), and 5.5% (95% CI 4.0%-7.4%) for L+RT, M+RT, and M, respectively (M+RT vs L+RT: HR 0.43, P <.001; M vs L+RT: HR 0.88, P =.57). For 1 to 3 positive lymph nodes, LFR10 was 6.5% (95% CI 4.8%-8.9%), 4.1% (95% CI 2.4%-7.0%), and 4.3% (95% CI 2.9%-6.5%) in L+RT, M+RT, and M, respectively (M vs L+RT: HR 0.68, P =.14; M vs M+RT: HR 1.2, P =.6). Conclusion: Low 10-year LFRs were seen regardless of trastuzumab use. Differences in local therapy in patients with 1 to 3 positive lymph nodes did not appear to improve local control. Local therapy studies for HER2+ and other tumor characteristics are important as the role of local therapies continues to evolve.
AB - Background: The goal of this study was to assess the impact of trastuzumab on locoregional failure. METHODS: The analysis included 2763 patients with HER2-positive (HER2+) breast cancer who were randomly assigned to adjuvant doxorubicin (A), cyclophosphamide (C), paclitaxel (T) and trastuzumab (H) (arm A, AC→T [n = 922]; arm B, AC→T→H [n = 988]; arm C, AC→T+H→H [n = 853]). Radiotherapy was given after AC→T concurrently with H. Radiotherapy was given after lumpectomy (L) or after mastectomy (M) with ≥4 positive lymph nodes but was optional for 1 to 3 positive lymph nodes. Locoregional failures at 10 years (LFR10) as first events were compared using competing risk analysis. Results: The median follow-up was 13.0 years. The first site of failure was local-only in 96 cases, locoregional in 16 cases, regional in 32 cases, and not specified in 2 cases; LFR10 was 4.8% (95% CI 4.1%-5.7%). LFR10 was 5.5% (95% CI 4.3%-7.2%), 4.9% (95% CI 3.7%-6.4%), and 2.8% (95% CI 1.9%-4.1%) in arms A, B, and C (B vs A: hazard ratio [HR] 0.91, P =.62; C vs A: HR 0.72, P =.12). For estrogen receptor–positive patients, LFR10 was 3.7% (95% CI 2.8%-4.8%) and for estrogen receptor–negative patients, it was 6.1% (95% CI 5.0%-7.4%; HR 0.61, P =.004). Local treatment included L+RT (n = 1044 [38%]), M+RT (n = 1025 [37%]), and M (n = 694 [25%]). LFR10 was 6.% (95% CI 5.0%-7.8%), 3.0% (95% CI 2.1%-4.3%), and 5.5% (95% CI 4.0%-7.4%) for L+RT, M+RT, and M, respectively (M+RT vs L+RT: HR 0.43, P <.001; M vs L+RT: HR 0.88, P =.57). For 1 to 3 positive lymph nodes, LFR10 was 6.5% (95% CI 4.8%-8.9%), 4.1% (95% CI 2.4%-7.0%), and 4.3% (95% CI 2.9%-6.5%) in L+RT, M+RT, and M, respectively (M vs L+RT: HR 0.68, P =.14; M vs M+RT: HR 1.2, P =.6). Conclusion: Low 10-year LFRs were seen regardless of trastuzumab use. Differences in local therapy in patients with 1 to 3 positive lymph nodes did not appear to improve local control. Local therapy studies for HER2+ and other tumor characteristics are important as the role of local therapies continues to evolve.
KW - HER2
KW - breast neoplasms
KW - radiotherapy
KW - trastuzumab
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U2 - 10.1002/cncr.33154
DO - 10.1002/cncr.33154
M3 - Article
C2 - 32931029
AN - SCOPUS:85090964546
VL - 126
SP - 5239
EP - 5246
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 24
ER -