HER2 Positivity at Diagnosis Shows Better PFS Benefit With HER2-Based Therapies Vs Negative Status in Breast Cancer

Author(s):

The median progression-free survival benefit experienced by patients with metastatic breast cancer who were HER2 positive at initial diagnosis and who were receiving standard HER2-directed therapies proved to be more favorable than what was reported in those who were HER2 negative and switched to HER2 positive status.

Hans-Christian Kolberg, MD, PhD

The median progression-free survival (PFS) benefit experienced by patients with metastatic breast cancer who were HER2 positive at initial diagnosis and who were receiving standard HER2-directed therapies proved to be more favorable than what was reported in those who were HER2 negative and switched to HER2 positive status, according to data from the PRAEGNANT trial (NCT02338167).

Results from the trial presented during the 2021 ASCO Annual Meeting demonstrated that those with HER2 positivity at baseline tended to have a longer PFS than those with HER2 negativity (hazard ratio [HR], 0.49; 95% CI, 0.24-1.03). These patients had a median observation time of 9 months (96% CI, 3.8-23.7) and 35 PFS events occurred over 4 years of observation.

Additionally, the PFS rates at 1 and 2 years proved to be lower in patients with HER2-negative disease. The HRs with regard to 1-year PFS rates in the HER2-negative and -positive populations were 0.26 (95% CI, 0.12-0.52) and 0.52 (95% CI, 0.36-0.73), respectively. At 2 years, the HRs for PFS in these groups were 0.19 (95% CI, 0.07-0.50) and 0.44 (95% CI, 0.29-0.67), respectively.

The median observation time for overall survival (OS) was 24.2 months (95% CI, 11.7-37.6). During 48 months of observation time, 12 events were reported; this meant that only the unadjusted model was calculable. No significant effect of HER2 status was reported (unadjusted HR, 0.49; 95% CI, 0.16-1.53; P = .22). However, patients with HER2-positive status at the time of their primary diagnosis tended to have longer OS than those who had negative status at that time point.

Slightly higher survival rates were observed for the HER2-positive group, as well. The HRs for 1-year OS in the HER2-negative and -positive groups were 0.77 (95% CI, 0.61-0.99) and 0.88 (95% CI, 0.79-0.99), respectively; the HRs for OS at 2 years in these groups were 0.67 (95% CI, 0.47-0.95) and 0.82 (95% CI, 0.70-0.97), respectively.

“Metanalyses have demonstrated that 5% to 10% of patients with initially HER2-negative disease switch to HER2-positive [status] through the course of the disease in the metastatic setting,” Hans-Christian Kolberg, MD, PhD, head of the Department of Obstetrics and Gynecology, Breast Cancer Center, and Gynecologic Cancer Center at Marienhospital Bottrop, Germany, said during a presentation on the data. “These patients are treated with the same HER2-directed approaches as those [who are] initially HER2 positive. However, it [has] not [been] known whether [these patients] benefit from those approaches in the same way [that their initially HER2-positive counterparts do].”

The prospective advanced breast cancer registry trial included data from 4061 patients; 49 of these patients met the inclusion criteria and were evaluated to see whether their baseline HER2 status of either negative or positive in their primary tumor had a prognostic value on OS and PFS following treatment with the HER2-directed agent, pertuzumab (Perjeta).

To be eligible for inclusion, patients needed to have histologically confirmed HER2neu–positive breast cancer with evidence of metastatic disease at the time of inclusion, the HER2 status of their primary disease had to be known, and they had to have previously received first-line therapy for metastatic disease.

If patients had negative or unknown HER2 status, received prior treatment with an investigational drug in a clinical study, or no observation time, they were excluded from the analysis.

Among the 49 patients included in the analysis, the median age was 56 years (range, 48-64), and all patients were women. The median body mass index was 25.2 (range, 22.8-30), and the median time from diagnosis to first-line therapy was 4.5 years (range, 3.2-8.6).

Moreover, 87.8% of had 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. In line 10 or 14, 59.2% of patients had been treated with chemotherapy, 6.1% were pretreated with pertuzumab, 44.9% were pretreated with trastuzumab (Herceptin), 2.0% were pretreated with ado-trastuzumab emtansine (Kadcyla; T-DM1), 2.0% were pretreated with lapatinib (Tykerb), and 55.1% were treated with antihormone therapy.

“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,” Kolberg concluded. “Our results [must be] interpreted with caution because of the small cohort and the prospective nature of the analysis; however, they definitely justify prospective research, including the group of initially HER2-negative patients who switched to HER2-positive [status] as a distinct entity.”

Reference

Kolberg H-C, Yüksel Öm Uhrig S, 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