Home > Oncology > ASCO 2020 > Breast & Ovarian Cancer > T-DM1 does not improve safety or efficacy in HER-2 positive early breast cancer; favorable iDFS reported

T-DM1 does not improve safety or efficacy in HER-2 positive early breast cancer; favorable iDFS reported

Presented by
Prof. N. Harbeck, University of Munich, Germany
ASCO 2020
Phase 3, KAITLIN
Findings from the primary analysis of the KAITLIN trial suggest that replacement of adjuvant taxane with trastuzumab emtansine (T-DM1) does not improve survival or safety for patients with HER2-positive early-stage breast cancer [1]. However, both treatments demonstrated outstanding long-term invasive diseasefree survival (iDFS) in a high-risk population. Study author Nadia Harbeck, MD, PhD, of the University of Munich, in Germany, and West German Study Group, presented these data during the ASCO20 Virtual Scientific Program.

HER2-positive early-stage breast cancer is a particularly aggressive, and neoadjuvant chemotherapy plus HER2-targeted therapy is the standard of care. Despite its efficacy, patients remain at increased risk of recurrence, mortality, and taxane-related toxicity, making it critical to optimize HER2-targeted treatment and determine who might benefit the most.

“In 2005, we were lucky to have one HER2-targeted therapy to combine with chemo[therapy] for patients with HER2-positive early-stage disease, and in 2020 we have four HER2-targeted agents available. However, clearly not everyone needs trastuzumab and chemotherapy,” discussant Sara A. Hurvitz, MD, of the University of California, Los Angeles, said. “We find ourselves in a bit of a Goldilocks conundrum, where we need to choose the therapy that is ‘just right’ for our patients.”

In an effort to help achieve this, the phase III KAITLIN trial compared survival and tolerability outcomes from the use of T-DM1 with pertuzumab versus standard of care.

Women with HER2-positive early-stage breast cancer received three to four cycles of adjuvant anthracycline (doxorubicin or epirubicin) and were then randomly assigned to either up to 18 cycles of T-DM1 (3.6 mg/kg) plus pertuzumab (420 mg; KP arm; 928 patients), or up to 18 cycles of trastuzumab (6 mg/kg) plus pertuzumab (420 mg) and three to four cycles of taxanes (THP arm; 918 patients). Primary endpoints were iDFS in the node-positive and intention-to-treat populations. Secondary endpoints were overall survival in both populations, disease-free survival, distant recurrence–free interval, safety, and patient-reported health status/quality of life.

There were no differences in iDFS between treatments in the node-positive and intention-to-treat groups. This was consistent across several subgroups (e.g., node status, central hormone receptor status, type of anthracycline, and geographic region). There was no clinically relevant subgroup that favored one study arm over the other.

“However, I think it’s noteworthy to look at the excellent 3-year iDFS in this high-risk population,” Dr. Harbeck said. “About 30% [of all patients] had more than four involved lymph nodes, but we see here about 93% iDFS in both [treatment] arms.”

The KP and THP regimens both demonstrated acceptable safety profiles, with comparable rates of grade 3 or greater adverse events (52% vs. 55%) and serious adverse events (21% vs. 23%). However, withdrawal from T-DM1 or trastuzumab because of adverse events was higher among patients receiving KP than those receiving THP (27% vs. 4%).

Finally, there was a lower risk of deterioration of patient-reported health status/quality of life in the KP group.

Dr. Hurvitz noted that re-examining KP versus THP but using a noninferiority study design would be beneficial and might have resulted in the primary endpoint being met. Not testing T-DM1 alone also represented a missed opportunity, she said.

However, Dr. Hurvitz emphasized that, despite failing to detect superiority among treatments, iDFS outcomes from the KAITLIN trial support those from the KRISTINE trial, which also examined T-DM1 plus pertuzumab, and improve upon survival outcomes from other node-positive/HER2-positive trials (Table) [2].
Table. Outcomes for LN+ HER+ disease with HER2-targeted adjuvant therapy from modern studies






Abbreviations: DFS, disease-free survival; LN, lymph node.


    1. Harbeck N, et al. ASCO Virtual Meeting, 29-31 May 2020, AbstractAbbreviations: DFS, disease-free survival; LN, lymph node.
    2. Hurvitz SA, et al. Lancet Oncol. 2018;19(1):115‐126.
    3. von Minckwitz G, et al. N Engl J Med. 2017;377(2):122‐131.
    4. Perez EA, et al. J Clin Oncol. 2011;29(25):3366‐3373.
    5. Slamon D, et al. N Engl J Med. 2011;365(14):1273‐1283.

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