medwireNews: Adjuvant treatment with trastuzumab emtansine (T-DM1) does not improve outcome or reduce toxicity relative to that with a taxane plus trastuzumab in patients with HER2-positive early breast cancer, results of the phase 3 KAITLIN study show.
Despite the trial not meeting its primary endpoint of improved efficacy with T-DM1, Nadia Harbeck, from the University of Munich (LMU) in Germany, told delegates at the virtual 2020 ASCO Annual Meeting that the 3-year invasive disease-free survival (IDFS) rates of 93–94% achieved with both treatments could be considered an “excellent” result in this high-risk population.
The study included 1846 patients with adequately excised, HER2-positive early breast cancer that was either lymph node positive or negative, hormone receptor-negative, and above 2.0 cm in size. Of these, 56% had between one and three positive lymph nodes and 34% had four or more positive nodes.
The patients were randomly assigned, within 9 weeks of surgery, to receive three to four cycles of anthracycline-based chemotherapy followed by 18 cycles of T-DM1 3.6 mg/kg plus pertuzumab 420 mg (loading dose 840 mg) every 3 weeks (n=928) or to a taxane plus concurrent trastuzumab 6 mg/kg (loading dose 8 mg/kg) and pertuzumab (n=918).
Adjuvant radiotherapy and/or endocrine therapy was administered after four cycles of HER2-targeted therapy where indicated.
Harbeck reported that, after a median 57 months of follow-up, there was no significant difference in IDFS rates between the two treatments in either patients who were lymph node positive or in the full intention-to-treat (ITT) population.
In the lymph node positive cohort (n=1658), 3-year IDFS was 92.8% among the patients who received T-DM1 and 94.1% among those who received a taxane plus trastuzumab. The corresponding rates in the ITT population were 93.1% and 94.2%, and Harbeck showed that the findings were consistent across all subgroups.
Harbeck also reported that the types and severity of adverse events (AEs) were similar to the known safety profiles of each treatment.
The incidence of grade 3 or higher AEs was 51.8% in the T-DM1 group and 55.4% in the taxane plus trastuzumab group, while serious AEs occurred in 21.4% and 23.3%, respectively.
In spite of these similarities, more patients discontinued T-DM1 than trastuzumab due to an AE, at 26.8% versus 4.0%.
The KAITLIN investigators also looked at patient-reported outcomes and found there was a significant 29% lower risk for deterioration in global health status from the start of HER-2 targeted therapy with T-DM1 than with a taxane plus trastuzumab, which the researchers attribute to taxane use.
Harbeck concluded that “adjuvant trastuzumab plus pertuzumab plus chemotherapy remains a standard of care for patients with high-risk HER-2 positive early breast cancer.”
Discussing the findings, Sara Hurvitz, from the University of California, Los Angeles in the USA, said that the “impressive [KAITLIN trial] deserves to be acknowledged.”
But she said that the universal use of anthracyclines in all patients was “a downside of the trial” when studies like TRAIN-2, also presented at the meeting and reported by medwireNews, question “whether we need anthracyclines.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group