Patient Summary: Adjuvant radiotherapy (RT) and trastuzumab in stage I-IIA breast cancer: Toxicity data from North Central Cancer Treatment Group Phase III trial N9831
NCCTG N9831 is a 3-arm randomized Phase III trial involving stage I-IIA breast cancer patients comparing the safety and efficacy of doxorubicin / cyclophosphamide (AC) followed by weekly paclitaxel vs the same chemotherapy with 1 yr of trastuzumab given either concurrently with paclitaxel or started after paclitaxel. Interim results of this trial have been previously reported. This report focused on the safety of administering radiation therapy in conjunction with trastuzumab, given its known cardiac toxicity and the close proximity of radiation to the heart.
The number of cardiac events was low in all three arms, with or without radiation therapy (0.7% without trastuzumab, 5.2% in the sequential trastuzumab arm, and 7.5% in the concurrent trastuzumab arm). Radiation (RT) did not increase the number of cardiac events in the groups receiving trastuzumab (2.5% with RT vs. 2.7% without RT in the sequential arm, 1.7% with RT vs. 5.8% without RT in the concurrent arm).
The main point of this abstract is that radiation therapy given concurrently with trastuzumab appears safe from a cardiac standpoint. This conclusion is limited by the fact that there is a relatively short amount of patient follow-up in this study (median follow-up 1.5 years). Radiation therapy is known to cause late appearing toxicities, and cardiac damage from radiation could manifest as far out as 10-15 years following treatment. Thus it seems somewhat premature to conclude that trastuzumab given concurrently with radiation is completely safe. When this data has matured, we will have a better idea as to the benefits and risks of these combination regimens.