Targit information

Evidence based information

In March 2000, an international, phase 3 randomised controlled trial was launched as a non- inferiority trial and over the years enrolled patients from 33 centres in ten countries. It compared outcomes in patients aged 45 years or older with invasive ductal carcinoma of Breast undergoing breast conserving surgery (BCS) followed by either whole breast external beam radiotherapy (EBRT) over several weeks or a riskadaptive approach using single-dose TARGIT.

Under the risk-adaptive approach, if the final pathology report demonstrated unpredicted prespecified adverse features, then EBRT was to be added to TARGIT afterwards, omitting boost radiation. The primary outcome measure in this study was local recurrence, with several secondary outcome measures including toxicity, survival, cosmesis, quality of life and health economics. Randomisation to the TARGIT or the EBRT arm was done either before lumpectomy (prepathology) or after lumpectomy (post- pathology).

Among the patients allocated to receive TARGIT, those in the pre-pathology group received it immediately after surgical excision under the same anaesthesia, while those in the post- pathology group received it as a subsequent procedure. the final recruitment goal of 3,451 women was achieved in June 2012 and the trial then closed to recruitment. The updated results were presented at the San Antonio Breast Cancer Symposium (Vaidya et al. 2012 ) (Table 1.1 ): 1,721 patients were randomly allocated to receive TARGIT and 1,730 to receive EBRT. 1,010 patients had a minimum of 4 years of follow-up and 611 patients had a minimum of 5 years of follow-up. Primary events (local recurrence) had increased from 13 to 34 since the Lancet publication.

For the primary outcome of ipsilateral breast recurrence (IBR), the absolute difference at 5 years was 2.0 %, which was higher with TARGIT and reached the conventional levels of statistical significance (p = 0.042), but was within the pre-specified non-inferiority margin; in the pre-pathology arm the absolute difference in 5-year IBR was 1 % and in the post-pathology arm it was higher, at 3.7 %. For the secondary outcome, there was a nonsignificant trend towards improved overall survival with TARGIT [HR = 0.70 (0.46–1.07)] due to fewer non-breast cancer deaths [17 vs. 35, HR 0.47 (0.26–0.84)]. Cardiovascular deaths were 1 vs. 10 and deaths from cancers other than breast were 7 vs. 16.

The results indicate that the risk-adapted approach using single-dose TARGIT had a slightly higher local recurrence rate than EBRT for the primary endpoint of IBR, but was within the preset non-inferiority boundary, with the prepathology group performing better than the postpathology stratum. In addition there was a trend towards improved overall survival in the TARGIT arm due to fewer non-breast cancer deaths. However, longer follow-up is needed to consolidate these findings.

A pilot of the cosmesis subprotocol in 118 patients indicated a superior cosmetic outcome in the first year for those receiving TARGIT (Keshtgar et al. 2010 ). Results from a pilot patient preference study of 58 patients confirmed that 54 (93 %) of the subjects would undergo TARGIT if it offered equivalent or some added risk compared with EBRT (Alvarado et al. 2010 ).