KAITLIN Trial: No Subgroup Benefits More From T-DM1 Plus Chemotherapy for HER2-Positive Early Breast Cancer

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In the phase III KAITLIN trial, replacing adjuvant taxane and trastuzumab with ado-trastuzumab emtansine (T-DM1) did not result in a significant improvement in invasive disease–free survival in the node-positive or intent-to-treat population of women with high-risk, HER2-positive early breast cancer.1 An updated biomarker analysis has now confirmed the lack of benefit with the newer regimen, in all subgroups of interest, as reported at the European Society for Medical Oncology (ESMO) Breast Cancer Virtual Congress 2021 by Otto Metzger, MD, Assistant Professor of Medicine at Harvard Medical School and the Dana-Farber Cancer Institute, Boston.2

Otto Metzger, MD

Otto Metzger, MD

KAITLIN enrolled 1,846 patients with HER2-positive hormone receptor–negative tumors greater than 2 cm and either node-positive or node-negative disease. After surgery, patients were randomly assigned to anthracycline-based chemotherapy followed by 18 cycles of T-DM1 plus pertuzumab or to a taxane plus concurrent trastuzumab and pertuzumab. The co-primary endpoints were invasive disease–free survival in the node-positive and intent-to-treat populations.

“Consistent with the primary study results, [T-DM1 plus pertuzu-mab] did not reduce the risk of an invasive disease–free survival event compared with [taxane plus concurrent trastuzumab and pertuzu-mab] in any biomarker subgroup,” Dr. Metzger reported. “Moreover, there was a trend toward worse outcomes with [T-DM1 plus pertuzumab] compared with [taxane plus concurrent trastuzumab and pertuzumab] in patients with lower HER2 gene copy number and focal HER2 expression, though the number of events was small.”

“No clear prognostic relationships were identified in pooled arms…. Trastuzumab plus pertuzumab and chemotherapy remains the standard of care for those with high-risk HER2-positive early breast cancer,” Dr. Metzger said.

“KAITLIN did not meet its primary endpoints; however, the 3-year invasive disease–free survival rates of 94% with [taxane plus concurrent trastuzumab and pertuzumab] and 93% with [T-DM1 plus pertuzumab] are notable in this high-risk population,” he added. These rates were seen in both the node-positive and intent-to-treat populations.

KAITLIN Biomarker Analysis

A preplanned exploratory analysis assessed the relationship between invasive disease–free survival and biomarkers potentially related to response: HER2 mRNA expression, PTEN immunohistochemistry expression, and activating PIK3CA hotspot mutations. These biomarkers were well balanced between treatment arms at baseline.


  • Biomarker analysis of the KAITLIN study revealed no subgroup who benefited more from anti-HER2 treatment with T-DM1 plus pertuzumab over trastuzumab/pertuzumab plus paclitaxel for the treatment of early HER2-positive breast cancer.
  • There was a trend toward worse outcomes, in fact, in the T-DM1 arm for two subgroups: patients with HER2 expression < 30% (ie, focal HER2 expression), with a hazard ratio of 2.77, and patients with HER2 gene copy number 4 to < 6, with a hazard ratio of 3.41.
  • For early HER2-positive breast cancer, adjuvant treatment with anthracycline/cyclophosphamide plus trastuzumab/pertuzumab and taxane remains the standard of care.

No biomarker subgroup showed more benefit from T-DM1 plus pertuzumab than taxane plus concurrent trastuzumab and pertuzu-mab. A trend toward reduced benefit with T-DM1 plus pertuzumab vs taxane plus concurrent trastuzumab and pertuzu-mab, in fact, was seen in two subsets of patients: (1) HER2 expression < 30% (ie, focal HER2 expression): hazard ratio [HR] = 2.77; and (2) HER2 gene copy number 4 to < 6: HR = 3.41. 

DISCLOSURE: Dr. Metzger has received honoraria from Grupo Oncoclinicas and Roche Brasil; has received institutional research funding from AbbVie, Cascadian Therapeutics, Eisai, Pfizer, Roche/Genentech, Susan G. Komen for the Cure, and the Breast Cancer Research Foundation. He has been reimbursed for travel, accommodations, or other expenses by Grupo Oncoclinicas.


1. Harbeck N, et al: Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer. ASCO20 Virtual Scientific Meeting. Abstract 500. Presented May 30, 2020.

2. Metzger O, et al: Biomarker analysis from KAITLIN, a randomised phase III study of adjuvant trastuzumab emtansine plus pertuzumab versus trastuzumab plus taxane plus pertuzumab after anthracyclines for high-risk HER2-positive early breast cancer. ESMO Breast Cancer Virtual Congress 2021. Abstract 420. Presented May 7, 2021.

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