Some breast cancer patients may not benefit from Herceptin

Some breast cancer patients may not benefit from Herceptin

15 Oct 2015

Prognosis for human epidermal growth factor receptor 2 (HER2)-positive patients with lymphocyte-predominant breast cancer (LPBC) was significantly better following treatment with chemotherapy alone than it was for their counterparts receiving chemotherapy plus trastuzumab (Herceptin). These are the results of an exploratory analysis of the North Central Cancer Treatment Group-N9831 trial.

Key findings of the analysis

A total of 2,027 patients were enrolled in N9831 and a subset of 945 patients was included in the stromal tumor-infiltrating lymphocytes (STILs) analysis. Patients had a median follow–up of 4.4 years. Patients without recurrent disease were observed for a median of 6.9 years.

In particular, the explanatory analysis revealed that:

• Among 489 patients from the N9831 trial receiving chemotherapy alone, 10-year Kaplan-Meier estimates for recurrence-free survival (RFS) among participants with high-levels of STILs was 90.9% compared with 64.5% for patients with low-levels of STILs.
• In dramatic contrast, 10-year estimates for RFS among 456 patients who received the same chemotherapy regimen followed by weekly paclitaxel plus trastuzumab followed by trastuzumab alone were virtually identical in patients with high- and low-levels of STILs at 80% and 80.1%, respectively.
• Adjusted for important prognostic variables including age, nodal status, hormone receptor status, tumor grade, and size, lymphocyte predominant breast cancer status was still significantly associated with 81% improvement in RFS in the chemotherapy alone arm but not in the arm in which trastuzumab was given.
• Hormone receptor status was also associated with a significant 37% improvement in RFS in the chemotherapy but not in the arm that contained additional trastuzumab.
• "There were 162 disease recurrence events: 8 events in the LPBC group and 154 in the non-LPBC group," investigators observed.
• Patients with LPBC tumors did not derive any additional benefit from the addition of trastuzumab.
• In contrast, patients with non-LPBC tumors did appear to derive benefit from additional trastuzumab.

“The analysis showed that patients did not benefit from the additional of trastuzumab”

"Analysis of HER2-positive cancers from patients enrolled in the FinHER adjuvant study has suggested that the levels of STILs are predictive of benefit from adjuvant trastuzumab therapy," Edith Perez, MD, Mayo Clinic, Jacksonville, Florida and colleagues write in JAMA Oncology.

"The goal of the present study was to determine whether the data from FinHER could be validated in a larger adjuvant trial with the standard 1 year of trastuzumab therapy such as N9831 [and] our findings do not show that increased levels of STILs, either assessed in deciles or dichotomously were predictive of increased benefit from adjuvant trastuzumab but rather that patients with high levels of STILs did not benefit from the additional of trastuzumab."

Limitations of the study

Even if results showed that patients with high levels of STILs did not benefit from the addition of trastuzumab, the authors caution that only 94 patients were classified as having LPBC and there were only eight disease recurrent events among this group. This means that this study was likely underpowered to detect a treatment effect in this group.

In an accompanying editorial, Sylvia Adams, MD, New York University School of Medicine, New York, points out that in triple negative breast cancer, results have consistently shown that increased tumor-infiltrating lymphocytes (TIL) at baseline are associated with reduced recurrence rates and an improved survival in women with early breast cancer receiving adjuvant chemotherapy.

Links between TILs and increased trastuzumab benefit

These results come from the Finland Herceptin (FinHER) trial in which Loi et al point out that they had 1,010 early-stage breast cancer patients, the majority of whom were HER2-negative but among the HER2-positive patients, some 232 were randomized to nine weeks of trastuzumab or no trastuzumab in addition to chemotherapy.

FinHER trial investigators concluded that their findings further support the idea that high levels of TILs should be considered as both a robust prognostic factor in triple negative disease as well as a signal of increased trastuzumab benefit in HER2-positive disease.

Contradictory results require further investigation

As Adams suggested, the difference between findings from the FinHER study regarding the benefit of trastuzumab in HER2-positive patients and its lack of benefit in the same group of patients in the current study may be traced back to hormone receptor status.

"Distribution of TILs varies significantly when HER2-positive tumors are divided into HR-positive and HR-negative tumors," Adams writes. "Clearly these contradictory predictive findings require further study and evaluation of additional data sets," Adams observed. "And further study of TILs as a predictive biomarker for HER2-positive breast cancer is required, ideally stratified by the HR subset."

Source: MedPage Today