pCR Further Validated as Predictor of Outcomes in HER2+ Breast Cancer

Pathologic complete response rate (pCR) was further validated as a predictor of outcomes in patients with HER2-positive breast cancer, particularly those who are hormone receptor (HR)-positive, according to findings from a meta-analysis published in ESMO Open.

Compared with patients who had residual disease, investigators reported that those who experienced a pCR had an improved recurrence-free survival (RFS; HR, 0.45; 95% CI, 0.34-0.60) and overall survival (OS; HR, 0.32; 95% CI, 0.22-0.48) for all combined treatments included in the analysis. In the population of patients with HR-negative disease, achievement of pCR was associated with a reduction in risk of relapse (65%) or death (73%).The HR-positive population also had an improvement in RFS following pCR, although less than the HR-negative population.

“As expected, in the present meta-analysis, we confirmed pCR to be strongly associated with prognosis…. This finding strengthens the already solid evidence supporting the role of pCR as a prognostic biomarker for single patients with HER2-positive [breast cancer] receiving chemotherapy [plus] HER2-targeted agents in the neoadjuvant setting. Notably, although pCR was found to be positively associated with long-term outcome in both [HR]-positive and [HR]-negative patients, the strength of the association was greater in this latter subgroup,” the authors wrote.

The systemic review used data from phase 2 and 3 randomized studies assessing lapatinib (Tykerb) plus neoadjuvant trastuzumab (Herceptin) and chemotherapy in patients with HER2-positive early breast cancer. A database search turned up 1794 records, of which 54 were assessed and 4 were included in the quantitative synthesis.

A total of 1410 patients were assessed as part of the survival analysis. In the population, investigators reported that dual HER2 blockade plus trastuzumab and lapatinib was successful in producing significantly improved RFS (HR, 0.62; 95% CI, 0.46-0.85). Moreover, dual blockade and lapatinib plus trastuzumab in addition to neoadjuvant chemotherapy was effective in improving OS vs trastuzumab alone (HR, 0.65; 95% CI, 0.43-0.98).

“Besides the established role of lapatinib for HER2-positive advanced [breast cancer] management, the present meta-analysis demonstrated significant survival benefit of an escalated approach including neoadjuvant dual HER2 blockade with lapatinib and trastuzumab for HER2-positive, high-risk patients [with breast cancer]. Also, in view of the maturity of the follow-up of the studies included, our results get the basis for reconsidering the role of lapatinib in the early setting,” the investigators wrote.

Other findings from the study identified a positive association between pCR and RFS (HR, 0.35; 95% CI, 0.23-0.53), as well as pCR and OS (HR, 0.27; 95% CI, 0.15-0.47) in patients with HR-negative disease. A significant association was also observed in the HR-positive group between pCR and RFS (HR, 0.60; 95% CI, 0.37-0.97), as well as a borderline significant association with OS (HR, 0.52; 95% CI, 0.23-1.15).

Reference

Guarneri V, Griguolo G, Miglietta F, et al. Survival after neoadjuvant therapy with trastuzumab–lapatinib and chemotherapy in patients with HER2-positive early breast cancer: A meta-analysis of randomized trials. ESMO Open. 2022;7(2):100433. doi:10.1016/j.esmoop.2022.100433