KEY TAKEAWAYS
- The PALLAS phase III trial aimed to evaluate HER2-low as a prognostic and predictive biomarker for palbociclib benefit in PALLAS trial participants.
- Despite geographic differences in HER2-low classification, palbociclib offered no distinct benefit and both HER2-0 and HER2-low tumors had similar outcomes in the trial.
HER2-low, indicating low levels of HER2 expression, has become a noteworthy therapeutic target in breast cancer (BC) patients, offering new treatment possibilities.
Guilherme Nader-Marta and his team aimed to assess clinical and demographic variables linked to HER2 expression and determine the prognostic and predictive role of HER2-low as a biomarker for palbociclib benefit in PALLAS trial participants.
The study explored palbociclib’s addition to adjuvant endocrine therapy in stage II-III hormone receptor-positive BC patients. This analysis evaluated the prognostic value of HER2-low status on invasive disease-free survival (IDFS), distant relapse-free survival (DRFS), and overall survival (OS), and determined HER2 expression’s predictive value for palbociclib response. HER2-low is defined as HER2 immunohistochemistry (IHC) 1+ or IHC 2+ with negative in situ hybridization; local pathologic evaluation was conducted.
Patients with HER2-0 and HER2-low BC were included, excluding those with HER2-positive cancer or missing HER2 status. Chi-squared tests assessed associations, and Cox Models evaluated prognostic and predictive power, with multivariable models considering age, T-stage, N-stage, grade, and progesterone receptor (PR) expression. HR and 95% CI were reported.
From the original PALLAS intention-to-treat (ITT) population (N = 5,753), this analysis included 5,304 patients (92.2%). Among them, 2,254 patients (42.5%) were classified as HER2 IHC 0 (HER2-0), and 3,050 (57.5%) as HER2-low (1,838 with IHC 1+ and 1,212 with IHC 2+). The median follow-up was 59.8 months.
Compared to HER2-0, patients with HER2-low tumors showed statistically higher estrogen receptor expression (mean expression 89.2% vs 88.2%, P = 0.019) and lower progesterone receptor expression (65.9% vs 68.2%, P = 0.007). Notably, HER2-low status varied significantly across 21 participating countries (range 16.7% to 75.6%, P < 0.001), being more frequent in North America (63.1%) than in Europe (53.4%) and other regions (53.4%) (P < 0.001).
No differences in HER2 expression were observed based on anatomic stage, T-stage, N-stage, histological grade, age, menopausal status, primary surgery type, prior radiation, prior chemotherapy, or baseline performance status. In univariate and multivariable Cox models, no statistically significant differences were found in IDFS, DRFS, or OS based on HER2 status (prognostic value). There was no significant interaction between HER2 status and the benefit of palbociclib in IDFS, DRFS, or OS. Similar results were obtained when HER2-0 was compared to HER2 1+ and HER2 2+ separately.
The results showed no discernible differences in clinical parameters, prognosis, or the predictive value of palbociclib between HER2-0 and HER2-low tumors in this extensive international cohort. Significant geographic variability in the prevalence of HER2-low status indicated variations in the pathologic assessment of HER2 expression without impacting outcomes. Research was sponsored by Alliance Foundation Trials, LLC.
Source: https://atgproductions.net/atgclients/sabcs/2023_SABCS_Abstract_Report-12-1-23_Compressed.pdf
Clinical Trial: https://clinicaltrials.gov/study/NCT02513394
Nader-Marta GN, Singer C, Hlauschek D, et al.(2023) ‘’Clinical characterization, prognostic and predictive values of HER2-low in early breast cancer in the PALLAS trial.’’ Presented at SABCS 2023 (PO1-01-13).
