HER2+ Status at Diagnosis in Patients With mBC Shows More Favorable PFS Than HER2-Negative Status

A prospective analysis demonstrated a trend toward worse prognosis for patients with metastatic breast cancer (mBC) who were initially HER2 negative and switched to HER2 positive treated with HER2-directed therapies compared with those who were HER2 positive at diagnosis.

“Metanalyses have demonstrated that 5% to 10% of patients with initially HER2-negative disease switch to HER2 positive through the course of the disease in the metastatic setting,” Hans-Christion Kolberg, MD, PhD, said during a presentation of the data at the 2021 American Society of Clinical Oncology Annual Meeting. “These patients are treated with the same HER2-directed approaches as patients initially HER2 positive. Although, it is not known if they benefit from those approaches the same way.”

In the advanced breast cancer registry trial PRAEGNANT (NCT02338167), 49 patients with HER2-positive mBC fit the inclusion criteria and were evaluated to see if their baseline HER2 status of either negative or positive in their primary tumor had a prognostic value on overall survival (OS) and progression-free survival (PFS) after treatment with pertuzumab (Perjeta).

There were 4061 patients registered to PRAEGNANT by January 2021, 59 of which had HER2-positive and metastatic disease. Patients were excluded if they had: negative or unknown HER2 status, therapy with an investigational drug in a clinical study, unknown date of first metastasis, no documented therapies, and unknown HER2 primary tumor status. From that group, 10 patients who had no observation time were excluded.

For these patients, there was a median observation time of 9 months (96% CI, 3.8-23.7). Thirty-five PFS events occurred over 4 years of observation. HER2 status at baseline showed no significant effect, with a likelihood ratio test P value of .07. Patients with initially HER2-positive disease had a longer PFS survival time compared with patients with initially HER2-negative disease (adjusted HR, 0.49; 95% CI, 0.24-1.03; P = .06). The 1- and 2-year PFS rates were lower for patients who were HER2 negative at diagnosis, with a median PFS of 7.8 months in the negative group and 10.0 months in the positive group.

The OS median observation time was 24.2 months (95% CI, 11.7-37.6). During 48 months of observation time, 12 events occurred, which meant only the unadjusted model was evaluable. There was no significant effect of HER2 status (unadjusted HR, 0.49; 95% CI, 0.16-1.53; P = .22). However, patients with positive HER2 status at primary diagnosis tended to have longer OS than those who were negative at diagnosis. There were slightly higher survival rates for the HER2-positive group as well.

According to Kolberg, the lead author of the analysis, “The number of patients switching from HER2 negative to HER2 positive in this analysis was higher than is known from the analysis published before and the median PFS, the 1-year, and the 2-year PFS rates appear to be better in patients initially HER2 positive.”

There were 43 patients (87.8%) with hormone receptor-positive status. Thirty-four patients had HER2-positive primary tumors, 9 had luminal A like tumors, and 6 had luminal B-like tumors. There were 29 of the 49 patients treated with chemotherapy, 3 who received pretreatment with pertuzumab, 22 pretreated with trastuzumab (Herceptin), 1 pretreated with TDM1, 1 pretreated with lapatinib (Tykerb), and 27 treated with antihormone therapy, all in either line 10 or 14.

The median age in this analysis was 56 years (range, 48-64) and all of the patients were women. There was a median body mass index of 25.2 (range, 22.8-30). The median time from diagnosis to first-line therapy was 4.5 years (range, 3.2-8.6).

“Our results have to interpret with caution because of the small cohort and the prospective nature of the analysis, but they definitely justify a prospective research, including the group of initially HER2 negative patients switch to HER2 positive as a distinct entity,” Kolberg concluded.

_Reference:

_{Kolberg H-C, Yüksel Ö, Fasching PA, et al. Comparison of therapy benefit from standard anti-HER2 directed approaches in metastatic breast cancer (MBC) between initially HER2-positive patients and patients initially HER2-negative with switch to HER2-positive. J Clin Oncol. 2021;39(suppl 15):1040. doi:10.1200/JCO.2021.39.15_suppl.1040}