Biomarker Data from the KAITLIN Study in High-Risk Early Breast Cancer

Evaluation of invasive disease-free survival (IDFS) according to biomarkers, including HER2 expression, the presence or absence of PIK3CA mutations, and others showed no advantage with treatment comprising anthracyclines (AC) followed by adjuvant trastuzumab-emtansine (TDM-1; K) plus pertuzumab (P) – AC-KP over the standard-of-care at the time the study was initiated, in particular adjuvant therapy of AC plus taxane (T), and trastuzumab (H) plus pertuzumab – AC-THP in patients with HER2-positive early breast cancer and high risk of disease recurrence. These findings from a biomarker analysis of data from the phase III KAITLIN study were presented at the ESMO Breast Cancer Virtual Congress 2021, held 5 to 8 May.

Otto Metzger of the Breast Oncology Centre, Dana Farber Cancer Institute, Harvard Medical School in Boston, USA presented the results of the preplanned exploratory biomarker analysis of data from the randomised, phase III KAITLIN study (NCT01966471).

This study compared patients with HER2-positive, high-risk early breast cancer treated with adjuvant AC-KP (n=928) versus AC-THP (n=918). This analysis assessed the relationship between IDFS and specific biomarkers that could potentially be related to response.

For the biomarker analysis, tumour samples were obtained at baseline for central assessment of HER2 status and pre-specified biomarkers that included determination of HER2 mRNA expression, activating PIK3CA hotspot mutations, and PTEN expression by immunohistochemistry (IHC) using a median cut-off.

The treatment effect on IDFS was investigated in biomarker subgroups.

Dr Metzger noted that a larger difference between the control AC-THP group compared to the AC-KP group in the 3-year IDFS rate was seen in the cohort of patients with focal HER2 expression (ie, HER2 IHC2+ and IHC3+ expression in less than 30% of the tumour tissue) and in the subgroup of patients having HER2 gene copy number of 4 to <6. Three-year IDFS in patients with focal HER2 expression was 97% in patients receiving AC-THP compared to 91.1% in patients receiving AC-KP (hazard ratio [HR] 3.41, 95% confidence interval [CI] 1.10-10.60). Similarly, 97.4% versus 87% of patients having HER2 gene copy number of 4 to <6 attained 3-year IDFS with AC-THP versus AC-KP, respectively.

The investigators were unable to determine clear prognostic relationships of biomarkers in pooled arms, such as in patients with PIK3CA mutation compared to those with non-mutated PIK3CA (HR 1.27, 95% CI 0.92–1.74).

In the PIK3CA mutated cohort, 3-year IDFS was 95.9% with AC-THP versus 89.7% with AC-KP (HR 1.31, 95% CI 0.78-2.20) and 3-year IDFS was 93.7% versus 94.1% in patients with non-mutated PIK3CA treated with AC-THP versus AC-KP, respectively.

Additionally, no prognostic relationships were observed in cohorts with higher HER2 expression (IHC3+) versus those with lower (IHC2+) HER2 expression (HR 0.82, 95% CI 0.55–1.23), or HER2 mRNA ≥ the median versus < the median (HR 0.76, 95% CI 0.56–1.03).

Regarding survival, 3-year IDFS in patients with lower HER2 expression by IHC (2+) was attained by 95.2% with AC-THP compared to 93.5% of patients with AC-KP (HR 1.34) and 3-year IDFS rates were 94.1% versus 93.2% with AC-THP versus AC-KP, respectively, in patients with HER2 IHC3+ expression (HR 0.89, 95% CI 0.64-1.24). Similarly, 3-year IDFS rates with the respective treatments were 94.6% versus 94.3% (HR 0.86) in patients with HER2 mRNA ≥ the median and 94.5% versus 91.7% in patients with < the median HER2 mRNA expression  (HR 1.18, 95% CI 0.79-1.77).

Dr. Evandro de Azambuja of the Jules Bordet Institute in Brussels, Belgium who discussed the study findings said that no biomarker byond HER2 itself has demonstrated clinical utility in HER2-positive breast cancer.


The authors pointed out that the biomarker analysis provided results that were consistent with those of the primary study results, which demonstrated that AC-KP did not reduce the risk of an IDFS event compared to AC-THP in any subgroup of patients defined by various patient and disease characteristics.

Based on these results, Dr Metzger concluded that pertuzumab and trastuzumab in combination with chemotherapy in the adjuvant setting remains the standard-of-care for patients with HER2-positive early breast cancer at high risk of recurrence.

The study was funded by F. Hoffmann-La Roche.


42O – Metzger O, Lambertini C, Krop IE, et al. Biomarker analysis from KAITLIN, a randomised phase 3 study of adjuvant trastuzumab emtansine (TDM-1; K) plus pertuzumab (P) versus trastuzumab (H) plus taxane (T) plus P after anthracyclines (AC) for high-risk HER2-positive early breast cancer (EBC). ESMO Breast Cancer Virtual Congress 2021 (5-8 May).