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

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.

Fig 1.

N9831 random assignment schema: H, trastuzumab in 4 mg/kg loading dose followed by 2 mg/kg; A, doxorubicin 60 mg/m²; C, cyclophosphamide 600 mg/m²; T, paclitaxel 80 mg/m²; HRT, hormone replacement therapy; RT, radiotherapy; qw, every week; q3w, every 3 weeks.

Fig 2.

Cumulative incidence plots of cardiac events after completion of paclitaxel (T) therapy by treatment arm and radiotherapy (RT) status (yes v no/unknown). A, doxorubicin; C, cyclophosphamide; H, trastuzumab.

Fig 3.

Cumulative incidence of cardiac events after completion of paclitaxel (T) therapy by treatment arm and side treated with radiotherapy (RT). (*) Right-sided RT or no/unknown RT. A, doxorubicin; C, cyclophosphamide; H, trastuzumab.