Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831

J Clin Oncol. 2009 Jun 1;27(16):2638-44. doi: 10.1200/JCO.2008.17.9549. Epub 2009 Apr 6.

Abstract

Purpose: To assess whether trastuzumab (H) with radiotherapy (RT) increases adverse events (AEs) after breast-conserving surgery or mastectomy.

Patients and 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / radiotherapy
  • Adenocarcinoma / surgery
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / surgery
  • Breast Neoplasms / therapy*
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Mastectomy*
  • Mastectomy, Segmental*
  • Middle Aged
  • Odds Ratio
  • Paclitaxel / administration & dosage
  • Radiotherapy, Adjuvant / adverse effects
  • Risk Assessment
  • Time Factors
  • Trastuzumab
  • Treatment Outcome
  • United States
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Doxorubicin
  • Cyclophosphamide
  • Trastuzumab
  • Paclitaxel