Tumor-infiltrating lymphocytes may predict response after HER-2 blockade therapy

CHICAGO — Tumor-infiltrating lymphocyte levels were lower baseline but higher at time of surgery among women with HER-2–amplified early-stage breast cancer who did not achieve a pathologic complete response after dual blockade therapy, according to an analysis of data from the TRYPHAENA study presented at the ASCO Annual Meeting.

There are no data concerning the potential association between the presence of tumor-infiltrating lymphocytes (TILs) at surgery after dual HER-2 blockade-based treatment and pathologic complete response (pCR).

“We wanted to address two questions: Is there any association between stromal TILs at diagnosis and pCR after optimal anthracycline–taxane or carboplatin–taxane neoadjuvant chemotherapy with HER-2 blockade?” Michail Ignatiadis, MD, PhD, attending oncology physician at Jules Bordet Institute in Brussels, said during his presentation. “And, is there any association between stromal TILs at surgery and pCR?”

Ignatiadis and colleagues measured stromal TILs prior to HER-2 blockade therapy, as well as at time of surgery, for 225 women enrolled in the phase 2 TRYPHAENA study.

Researchers of the TRYPHAENA study randomly assigned women to trastuzumab (Herceptin, Genentech) and pertuzumab (Perjeta, Genentech), concurrently or sequentially, with an anthracycline regimen; or concurrently with an anthracycline-free regimen.

A mean of two independent reviewers calculated stromal TIL percentages and scored TILs according to consensus guidelines published in Annals of Oncology.

One hundred thirty-one women (58.2%) achieved pCR. The researchers associated an increase of log stromal TILs at baseline with an increased probability of pCR (coefficient estimate: 0.31; 95% CI, 0.03-0.59) in a univariate analysis, with a trend toward association after clinicopathological adjustment (coefficient estimate: 0.3; 95% CI, –0.05 to 0.64).

Increased log stromal TILs at the time of surgery (n = 140) appeared associated with a lower probability of pCR in a univariate analysis (coefficient estimate: –0.44; 95% CI, –0.75 to –0.13), and remained associated after adjustments (coefficient estimate: –0.6; 95% CI, –1 to –0.2).

Study limitations included the lack of evaluable TILs surgical samples from 40% of patients, as well as the lack of long-term clinical outcomes data, such as EFS.

Further, because all patients included in the study received HER-2 blockade therapy, the researchers could not examine biomarker questions related to single vs. dual blockade therapy.

“In patients that received optimal chemotherapy and HER-2 blockade therapy, stromal TILs as a continuous variable at diagnosis were associated with increased pCR in multivariate analysis,” Ignatiadis said. “However, the clinical utility of TILs at diagnosis to predict pCR is not supported by the present study. We did demonstrate for the first time that patients who did not achieve pCR at the time of surgery had higher stromal TILs at surgery, compared with pCR patients.”

Ignatiadis stated that the present research has led to further research questions that should be addressed in future studies.

“There are several open research questions,” Ignatiadis said. “What is the TIL immunophenotypic composition in patients with high TILs at diagnosis and/or at surgery who did not achieve pCR? What is the role of immune checkpoint inhibitors or other immunotherapeutic approaches in these patients?” – by Cameron Kelsall

Reference:

Ignatiadis M, et al. Abstract 11507. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclosure: Ignatiadis reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.