Concurrent Trastuzumab and Radiation Therapy (RT) in the Adjuvant Treatment of Breast Cancer

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 18, 2005

Presenter: J. R. Bellon
Presenter's Affiliation: Dana-Farber Cancer Institute
Type of Session: Scientific

Background

Her-2-Neu is overexpressed in approximately 25% of breast cancer patients and confers a worse prognosis. Adjuvant trastuzumab improves outcome in node-positive breast cancer patients with Her-2-Neu positivity and high risk node-negative patients with Her-2-Neu positivity. Systemic treatment concurrent with radiotherapy is a potentially desirable option as neither treatment is delayed, and systemic therapy may enhance radiation effects on tumor cells. However, increased acute toxicity associated with concurrent treatment is well-documented. This study was undertaken to evaluate acute toxicity when trastuzumab is given concurrently with radiation.

Materials and Methods

26 patients with Stage II or III breast cancer receiving trastuzumab with concurrent radiation between August 2001 and February 2004 were retrospectively analyzed
21 patients received weekly trastuzumab (2 mg/m2) and 5 patients received trastuzumab every 3 weeks (6 mg/m2)
All patients received doxorubicin-based chemotherapy prior to the start of radiation, and median duration from last chemotherapy cycle to start of radiation was 4 weeks
5 patients received tangential radiation alone, and 21 patients received an additional supraclavicular field (10 of the 21 patients also received axillary radiation)
10 patients were status post breast conservation and received 60-61 Gy to the primary site; 16 patients were status post mastectomy and received 50.4 Gy to the chest wall and all had anterior nodal fields; 3 of the 16 patients also received radiation to the internal mammary nodes

Results

Median follow-up for all patients was 26 months (range 6-37 months)
2 patients (8%) developed grade 2 radiation pneumonitis approximately 2 weeks following the end of RT; both had CT changes correlating to radiation portals and neither required steroids
Both pneumonitis patients received weekly trastuzumab and chest wall irradiation (one with an electron boost to the incision site for an additional 10 Gy) as well as a supraclavicular field
1 patient developed dyspnea on exertion and had bilateral patchy ground glass opacities on CT imaging; no specific treatment was advocated and the symptoms resolved over 2 months; a definitive diagnosis of pneumonitis was not made
12 patients (46%) developed grade 1 skin toxicity, 12 patients (46%) developed grade 2 skin toxicity, and 2 patients (8%) developed grade 3 toxicity; no grade 4 skin toxicity was observed

Author's Conclusions

Delivery of trastuzumab concurrent with radiation treatment resulted in acceptable acute toxicity
Although the rate of pneumonitis (8%) was higher than that observed with sequential treatment, it was similar with rates found in previous concurrent chemoradiation series
Both pneumonitis cases occurred earlier than would be expected for radiation-associated pneumonitis

Clinical/Scientific Implications

This small retrospective study with short follow-up documented an acceptable acute toxicity profile for trastuzumab delivered concurrently with radiation. There is significant interest in adding biologic therapies to radiation therapy concurrently. Future prospective studies are warranted to more fully quantify the risk of both acute and late toxicity as well as outcomes related to local and systemic disease control.