The 5-year results of the TARGIT-A trial have demonstrated the non-inferiority of risk-adapted, single-dose targeted intraoperative radiotherapy (TARGIT-IORT) delivered during lumpectomy to conventional radiotherapy for the adjuvant treatment of early-stage breast cancer.
Noting that “TARGIT-IORT has similar long term local control and cancer survival outcomes to whole breast radiotherapy,” the researchers say that “[s]ingle dose TARGIT-IORT during lumpectomy should be accessible to healthcare providers and discussed with patients when surgery for breast cancer is being planned.”
The phase 3 trial included 2298 women aged at least 45 years with clinical stage T1 or T2 (tumors ≤3.5 cm), N0–N1, M0 disease who were eligible for breast-conserving surgery. Prior to lumpectomy, participants were randomly assigned to receive a single dose of TARGIT-IORT during the surgical procedure or a standard postoperative daily fractionated course of whole-breast external beam radiotherapy (EBRT) over a period of 3–6 weeks.
At the 5-year mark, the local recurrence rate as estimated by binomial proportions was 2.11% for the immediate TARGIT-IORT group and 0.95% for the EBRT group. This equated to an absolute difference of 1.16 percentage points, which was within the predefined non-inferiority margin of 2.50 percentage points.
Non-inferiority of TARGIT-IORT in terms of local control was also confirmed using Kaplan–Meier estimates, which gave a between-group difference of 1.21 percentage points, report Jayant Vaidya, from University College London in the UK, and co-investigators in The BMJ.
And over a median follow-up of 8.6 years, no statistically significant differences were found for secondary endpoints such as invasive local recurrence-free, mastectomy-free, distant disease-free, breast cancer-specific, and overall survival.
In fact, the risk for mortality from causes other than breast cancer was a significant 41% lower for women who received TARGIT-IORT than those given EBRT, a finding consistent with other reports, including a meta-analysis of randomized trials, say the study authors.
They also highlight that “[around] 80% of patients required no additional radiotherapy after TARGIT-IORT,” an option that was permitted for women in the experimental group found to have unexpected higher risk factors on postoperative histopathologic analysis.
Speaking to medwireNews, Melvin Silverstein (Hoag Memorial Hospital Presbyterian, Newport Beach, California, USA), commented that the 5-year local recurrence rate reported with TARGIT-IORT is “incredibly low,” and therefore “risk-adapted TARGIT-IORT has the power to change future breast cancer care.”
He added that “IORT yields a better cosmetic result, is less expensive, is far more convenient, and will have a significant impact on the future of breast conservation.”
Another independent commentator – Joanne Haviland, from The Institute of Cancer Research in London, UK – provided a note of caution, however, highlighting “the longstanding concerns around the methodological and analytical weaknesses in the trial that undermine its results.”
Haviland told medwireNews that her concerns include “a different definition of primary outcome for the time-to-event analyses, which includes deaths as well as local recurrences,” for this versus previous reports from the trial. “This gives the misleading impression that local recurrence rates are very high in both randomized groups.”
She also pointed out that “the results in the manuscript only relate to patients who were randomized before surgery,” whereas “in the trial protocol and in previous publications, the pre- and post-surgery groups are described as strata within a single trial but, in this new paper, the two groups are now described as two parallel randomized controlled trials and reported separately.”
Haviland continued: “For the results of any clinical trial to be robust, the findings need to represent the entirety of the data collected.”
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