medwireNews: The latest results from the KATHERINE trial add support for the adjuvant use of trastuzumab emtansine (T-DM1) in people with HER2-positive early breast cancer and residual invasive disease.
As reported in The New England Journal of Medicine, the invasive disease-free survival (IDFS) benefit offered by the antibody–drug conjugate T-DM1 over trastuzumab was maintained with longer follow-up, and overall survival (OS) was also significantly improved.
The study authors explain that the primary analysis – done at a median follow-up of 40.9–41.4 months – showed a significant halving in the risk for invasive disease or death with T-DM1, but the OS analysis “did not cross the early reporting boundary.”
The current report focuses on the prespecified final analysis of IDFS and the second interim analysis of OS, conducted at a median follow-up of 100.8–101.4 months, they continue.
Among patients with HER2-positive early breast cancer and residual invasive disease in the breast or axilla at surgery after neoadjuvant treatment with taxane-based chemotherapy plus trastuzumab, the estimated 7-year IDFS rate was 80.8% for the 743 patients who were randomly assigned to receive up to 14 cycles of adjuvant T-DM1 at a dose of 3.6 mg/kg every 3 weeks.
This was significantly higher than the rate of 67.1% for their 743 counterparts who instead received trastuzumab at a dose of 6 mg/kg every 3 weeks for 14 cycles, equating to an absolute difference between the groups of 13.7 percentage points.
The hazard ratio (HR) for invasive disease or death was 0.54 in favor of treatment with T-DM1.
OS was similarly significantly better with the use of T-DM1 rather than trastuzumab, with estimated 7-year rates of 89.1% and 84.4%, respectively. The absolute between-group difference was 4.7 percentage points and the HR for death was 0.66.
“The substantial improvements in long-term invasive disease–free survival and overall survival were present irrespective of the extent of disease at presentation, hormone-receptor status, whether neoadjuvant chemotherapy was administered with trastuzumab alone or with an additional HER2-targeted agent, pathological nodal status at surgery, age cohorts, and race,” note the investigators.
But they point out that the T-DM1 benefit was less marked for patients with an immunohistochemical (IHC) score of 2+ versus those with an IHC 3+ score, with respective HRs relative to trastuzumab of 0.84 and 0.47.
Therefore, “the IHC 2+ subgroup remains a population in need of more effective therapy,” write Charles Geyer, Jr (UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA) and co-researchers.
Moving onto the safety findings, they say that “[b]ecause patients had already completed treatment at the time of the primary analysis, safety data at this update were as expected, and delayed toxic effects were rarely observed with adjuvant T-DM1.”
Over the entire trial period, grade 3 or worse adverse events (AEs) occurred in 26.1% of participants treated with T-DM1 and 15.7% of those given trastuzumab, while serious AEs were observed in a corresponding 12.7% and 8.1%.
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