Breast Cancer Coverage from Every Angle

Lessons From NALA: Biomarkers of Treatment Response in Metastatic Breast Cancer

By: Melissa Steele-Ogus
Posted: Wednesday, August 26, 2020

The phase III NALA trial compared two tyrosine kinase inhibitors used to treat patients with HER2-positive metastatic breast cancer who were previously unresponsive to two or more targeted treatments. The study found a better progression-free survival in patients who received neratinib than those who received lapatinib, both in conjunction with capecitabine.

Cristina Saura, MD, of the Vall d’Hebron Institute of Oncology, Barcelona, and colleagues further probed the NALA data to determine any relationship between progression-free survival and three biomarkers. They found PIK3CA mutations correlated with decreased survival, whereas both ERBB2 mutations and increased levels of HER2 protein were associated with increased survival. The results were published in Annals of Oncology.

A total of 420 patients were enrolled in the study; samples were taken from primary tissue in 283 patients and in secondary or lymph node tissue in 137 patients. Next-generation sequencing was used to identify mutations in ERBB2 and PIK3CA, and the results were confirmed by digital droplet polymerase chain reaction when available. HER2 expression was assessed as well.

PIK3CA mutations, which were identified in 148 patients (35%), correlated with a decreased progression-free survival (hazard ratio = 0.81; 95% confidence interval [CI] = 0.64–1.02; P = .077). In contrast, ERBB2 mutations, which were found in 26 patients (6.2%), had an increased progression-free survival (hazard ratio = 1.68; 95% CI = 0.97–3.29; P = .086); however, the study authors noted the small sample size here. When treatment arms were combined, patients with higher HER2 protein expression had increased progression-free survival and were more responsive to the treatment regimen of neratinib and capecitabine than lapatinib and capecitabine.

Disclosure: For full disclosures of the study authors, see

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