Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831.
OBJECTIVE
To assess whether trastuzumab (H) with radiotherapy (RT) increases adverse events (AEs) after breast-conserving surgery or mastectomy.


METHODS
Patients with early-stage resected human epidermal growth factor receptor 2 (HER-2) -positive breast cancer (BC) were randomly assigned to doxorubicin (A) and cyclophosphamide (C), followed by weekly paclitaxel (T; AC-T-H or AC-TH-H). RT criteria (with or without nodal RT) were postlumpectomy breast or (optional) postmastectomy chest wall. RT of internal mammary nodes was prohibited. RT commenced within 5 weeks after T, concurrently with H. Analysis included 1,503 irradiated patients for RT-associated AEs across treatment arms. Rates of cardiac events (CEs) with and without RT were compared within arms.


RESULTS
No significant differences among arms were found in incidence of acute skin reaction, pneumonitis, dyspnea, cough, dysphagia, or neutropenia. A significant difference occurred in incidence of leukopenia, with higher rates for AC-T-H versus AC-T (odds ratio = 1.89; 95% CI, 1.25 to 2.88). At a median follow-up of 3.7 years (range, 0 to 6.5 years), RT with H did not increase relative frequency of CEs regardless of treatment side. The cumulative incidence of CEs with AC-T-H was 2.7% with or without RT. With AC-TH-H, the cumulative incidence was 1.7% v 5.9% with or without RT, respectively.


CONCLUSIONS
Concurrent adjuvant RT and H for early-stage BC was not associated with increased acute AEs. Further follow-up is required to assess late AEs.
Halyard
Michele Y
MY
Mayo Clinic Scottsdale, Scottsdale, AZ 85259, USA. mhalyard@mayo.edu
Pisansky
Thomas M
TM
Dueck
Amylou C
AC
Suman
Vera
V
Pierce
Lori
L
Solin
Larry
L
Marks
Larry
L
Davidson
Nancy
N
Martino
Silvana
S
Kaufman
Peter
P
Kutteh
Leila
L
Dakhil
Shaker R
SR
Perez
Edith A
EA
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008408:Mastectomy; D015412:Mastectomy, Segmental; D008875:Middle Aged; D016017:Odds Ratio; D017239:Paclitaxel / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D018570:Risk Assessment; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004317:Doxorubicin; D003520:Cyclophosphamide; D000068878:Trastuzumab; D017239:Paclitaxel