Cytotoxic TILs Appear Predictive of Outcomes in Metastatic HER2-Positive Breast Cancer
For patients with HER2-positive metastatic breast cancer, CD8-positive, cytotoxic tumor infiltrating lymphocytes may be predictive of outcomes after treatment with trastuzumab.
Low baseline levels of CD8-positive, cytotoxic tumor infiltrating lymphocytes (TILs) were predictive of a robust benefit from trastuzumab (Herceptin) vs lapatinib (Tykerb) in the first-line treatment of metastatic, HER2-positive breast cancer, according to a secondary analysis of the CCTG MA.31 phase 3 study (NCT00667251).
Although investigators reported that hematoxylin-eosin (H&E) stromal TIL (sTIL) counts higher than 5% were identified in 35% of the 647 patients included in the study, significant predictive and prognostic effects were not observed. However, the univariate stratified analyses identified that low (HR, 2.94; 95% CI, 1.40-6.17; P = .003) and high (HR, 1.36; 95% CI, 1.05-1.75; P = .02) CD8-positive sTIL counts were significantly predictive of progression on lapatinib compared with trastuzumab.
“Our findings suggest that investigating whether low preexisting immune infiltrate levels identify a group of patients better treated with antibody-based therapies may be worthwhile, not only for breast cancer but also for other types of cancer,” the investigators wrote.
The trial ran from January 17, 2008, to December 1, 2011, and enrolled patients with HER2-positive metastatic breast cancer across 21 countries. Patients were randomized 1:1 to receive either trastuzumab plus a taxane for 24 weeks followed by 6 mg/kg of trastuzumab every 3 weeks or lapatinib at a 1500 mg daily dose. In terms of taxanes, patients could receive either 80 mg/m2 of intravenous paclitaxel once weekly or intravenous docetaxel at 75 mg/m2 every 3 weeks. The trial had a median follow up of 21.5 months.
TILs were assessed via H&E–stained whole sections. Among the available slides, 55.2% were from surgical excisions and 44.8% came from core needle biopsies. Patients on the study had a median age of 55.0 years. Among those who received treatment, investigators obtained immunohistochemistry results for 427 for CD8, 398 for FOX-P3, 394 for PD-1, and 372 for CD56.
Other findings from the study indicated that of the 614 tumors that were evaluable for overall H&E–stained TILs had a mean score of 9.2%. Among tissues samples from patients with metastatic disease, 2.3% had TIL scores that were at least 50%. Overall, counts of 5% or greater were noted in 35% of cases, although this was not considered to be prognostically significant or predictive.
Additionally, a univariate analysis indicated that none of the other assessed biomarkers, including CD8 (HR, 0.91; 95% CI, 0.67-1.24), FOXP3 (HR, 0.91; 95% CI, 0.70-1.18), PD-1 (HR, 0.90; 95% CI, 062-1.30), or TILs assessed through H&E–stained sections, significantly impacted progression-free survival. Similar findings were reported in terms of hormone receptor-positive and -negative subgroups.
Reference
Liu S, Chen B, Burugu S, et al. Role of cytotoxic tumor-infiltrating lymphocytes in predicting outcomes in metastatic HER2-positive breast cancer a secondary analysis of a randomized clinical trial. JAMA Oncol. 2017;3(11):e172085. doi:10.1001/jamaoncol.2017.2085
Treatment Combinations for HER2-Positive Breast Cancer
March 7th 2013As part of our coverage for the 30th Annual Miami Breast Cancer Conference, we bring you an interview with Dr. Mark Pegram, director of the breast cancer program at the Stanford Women’s Cancer Center and codirector of the molecular therapeutics program. Dr. Pegram will be discussing the potential for novel HER2 combination therapies at the conference.
