Adjuvant radiotherapy (RT) and trastuzumab in stage I-IIA breast cancer: Toxicity data from North Central Cancer Treatment Group Phase III trial N9831

Abstract

523 Background: Adjuvant trastuzumab (Herceptin [H]) with chemotherapy improves outcome in HER2+ breast cancer (BC). Preclinical studies suggest H may enhance RT. We herein assess if H given with adjuvant RT increases adverse events (AE) after breast conserving surgery or mastectomy. Methods: N9831 randomized 3505 women with pT1–3N1–2M0, pT2–3N0M0, or pT1cN0M0 (ER/PR negative) HER2+ BC to doxorubicin (A) and cyclophosphamide (C) followed by weekly paclitaxel (T), AC→T→H, or AC→TH→H. Post-lumpectomy breast ± nodal RT was recommended, as was post-mastectomy chest wall + nodal RT (>3 nodes +); internal mammary RT was prohibited. RT started within 5 weeks of completion of T and allowed concurrently with H. 2324 eligible patients were enrolled on study prior to April 25, 2004: 1460 patients receiving RT are available for analysis of RT-associated AEs. Also, 1286 patients on +H arms who completed T (908 +RT and 378 -RT) are available for analysis of clinical cardiac events (CE). Rates of RT-associated AEs were compared across treatment arms, and rates of CE were compared for +RT vs -RT patients within +H arms. All reported p-values are for chi-squared statistics. Results: With a median follow-up of 1.5 years, significant differences among arms in RT-associated AEs were not identified. No significant differences across arms in +RT patients existed in the incidence of skin reaction (p=0.78), pneumonitis (p=0.78), dyspnea (p=0.87), cough (p=0.54), esophageal dysphagia (p=0.26), or neutropenia (p=0.16). There was a significant difference in +RT patients in the incidence of leukopenia (p=0.02) with higher incidence rates in the arms receiving H. RT did not increase the frequency of CE. In the AC→T→H arm, the incidence of CE was 2.2% in +RT patients versus 2.9% in -RT patients. In the AC→TH→H arm, the incidence of CE was 1.5% in +RT patients versus 6.3% in -RT patients. No difference in CE was seen between left- and right-sided RT fields in +RT patients in either +H arm. Conclusion: Concurrent administration of adjuvant RT with H in early stage breast cancer patients is not associated with an increased incidence of acute RT AEs. Further follow-up is required to assess late AEs. No significant financial relationships to disclose.