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Biomarker Analysis of the KAITLIN Trial: No Subgroup Benefits More From T-DM1 Plus Chemotherapy


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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, as reported by Harbeck et al at the 2020 ASCO Virtual Scientific Program (Abstract 500).

An updated biomarker analysis of the trial has now confirmed the lack of benefit with the newer regimen in all subgroups of interest, as reported at the ESMO Breast Cancer Virtual Congress 2021 (Abstract 420) by Otto Metzger, MD, Assistant Professor of Medicine at Harvard Medical School and Dana-Farber Cancer Institute.

Otto Metzger, MD

Otto Metzger, MD

KAITLIN Details

KAITLIN enrolled 1,846 patients with HER2-positive, hormone receptor–negative breast tumors > 2.0 cm and either node-positive or node-negative disease. After surgery, patients were randomly assigned to receive anthracycline-based chemotherapy followed by 18 cycles of T-DM1 plus pertuzumab (AC-KP) or to a taxane plus concurrent trastuzumab and pertuzumab (AC-THP). The co-primary endpoints were invasive disease–free survival in the node-positive and intent-to-treat populations.

“Consistent with the primary study results, AC-KP did not reduce the risk of an invasive disease–free survival event compared to AC-THP in any biomarker subgroup,” Dr. Metzger reported. “Moreover, there was a trend toward worse outcomes with AC-KP compared with AC-THP 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 AC-THP and 93% with AC-KP 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 (IHC) expression, and activating PIK3CA hotspot mutations. These biomarkers were well balanced between treatment arms at baseline.

No biomarker subgroup showed more benefit from AC-KP than AC-THP. A trend for reduced benefit with AC-KP vs AC-THP, however, was seen in two subsets of patients:

  • HER2 expression < 30% (ie, focal HER2 expression): hazard ratio = 2.77
  • HER2 gene copy number 4 to < 6 gene copy: hazard ratio = 3.41.

No clear prognostic relationships were identified in the pooled-arms analysis, including PIK3CA mutated vs nonmutated tumors (hazard ratio [HR] = 1.27), HER2 IHC3+ vs IHC2+ (HR = 0.82) or HER2 mRNA ≥ vs > median (HR = 0.76).

The study authors concluded, “Consistent with the primary study results, AC-KP did not reduce the risk of an invasive disease–free survival event compared to AC-THP in any biomarker subgroup. HP + chemotherapy remains the standard of care for those with high-risk HER2-positive early breast cancer. No biomarkers had prognostic value in the pooled arm analyses.”

Disclosure: Dr. Metzger disclosed financial relationships with AbbVie, G1 Therapeutics, and Roche. For full disclosures of the study authors, visit oncologypro.esmo.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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