Tumor-Infiltrating Lymphocyte Analysis for Survival Outcomes in Early ERBB2-Positive Breast Cancer

In the 10-year follow-up analysis of the ShortHER randomized clinical trial, researchers examined whether the level of tumor-infiltrating lymphocytes (TILs) is associated with survival outcomes in patients with ERBB2 (formerly HER2)–positive early breast cancer and whether this can guide adjuvant treatment de-escalation. Results were published in JAMA Oncology.

In the multicentric Italian ShortHER trial, patients were randomly assigned to either 3 courses of taxanes combined with trastuzumab for 9 weeks followed by 3 courses of reduced-dose anthracycline-based chemotherapy (short arm) or 4 cycles of anthracycline-based chemotherapy followed by 4 courses of taxanes combined with trastuzumab for 1 year (long arm).

Of the 1,253 patients enrolled in this trial, 866 of them (median age, 56 years; interquartile range, 48-64 years) had evaluable TILs. In Cox models with relevant factors, each 5% increase in TIL increment was associated with improved distant disease-free survival (DDFS) (hazard ratio [HR], 0.87; 95% CI, 0.80-0.95; P=0.001) and overall survival (OS) (HR, 0.89; 95% CI, 0.81-0.98; P=0.01).

The 10-year OS rates were:

• 3% for patients with TILs ≥20%
• 3% for patients with TILs ≥30%
• 1% for patients with TILs ≥50%

Patients with TILs <20% showed a better outcome in the long arm than in the short arm (10-year DDFS, 88.7% vs. 81.0%), whereas for patients with TILs ≥20%, the 10-year DDFS was 87.1% in the long arm versus 92.2% in the short arm (P for interaction=0.01).

Patients with ≥20% TILs had a 10-year OS rate of 89.3% in the long arm versus 93.1% in the short arm (HR, 0.36; 95% CI, 0.10-1.36); patients with <20% TILs had a 10-year OS rate of 91.3% in the long arm versus 86.9% in the short arm (HR, 1.36; 95% CI, 0.82-2.23; P for interaction=0.06).

According to these data, TILs can serve as a biomarker to identify patients with ERBB2-positive early breast cancer who may safely undergo de-escalated adjuvant therapy without compromising long-term survival outcomes.

The researchers concluded that their follow-up analysis of the ShortHER trial is likely “the first demonstration of an independent effect of TILs in terms of OS for patients with ERBB2-positive early breast cancer treated with adjuvant chemotherapy and anti-ERBB2 therapy.” They pointed out that “Patients with TILs 20% or higher who de-escalated trastuzumab duration and chemotherapy dose were not exposed to an excess risk of distant relapse or death.”

Source

JAMA Oncology