In HER2+ Breast Cancer, Higher TIL Levels Associated With Improved OS

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In HER2+ Breast Cancer, Higher TIL Levels Associated With Improved OS
In HER2+ Breast Cancer, Higher TIL Levels Associated With Improved OS

SAN ANTONIO – In patients with advanced HER2-positive breast cancer treated with docetaxel plus trastuzumab in combination with pertuzumab or placebo, higher tumor-infiltrating lymphocyte (TIL) levels are significantly associated with improved overall survival, according to findings presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) and published simultaneous in The Lancet Oncology.1

“Retrospective analyses from clinical trials of early HER2-positive breast cancer have demonstrated significant associations of increasing TILs with improved pathologic complete response rates, event-free survival, disease-free survival, and overall survival,” said Stephen J Luen, MBChB, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia. “However, the prognostic association of TILs in the setting of advanced HER2-positive breast cancer is unknown.”

Therefore, researchers sought to evaluate the prognostic impact of host antitumor immunity as determined by baseline TIL levels in patients with advanced HER2-positive breast cancer treated with chemoimmunotherapy.

For the study, investigators analyzed data from 678 tumor samples of 808 participants of the phase 3 CLEOPATRA study (ClinicalTrials.gov Identifier: NCT00567190). In CLEOPATRA, patients with locally recurrent, unresectable, or metastatic HER2-positive breast cancer were randomly assigned to receive pertuzumab or placebo, in combination with first-line trastuzumab and docetaxel therapy.

“Age, tumor grade, and presence of visceral disease at screening were not significantly associated with TIL levels,” Dr Luen explained. “However, estrogen receptor (ER)-negative tumors had significantly higher TIL levels (P <.001) and TIL levels significantly differed by ethnicity (P <.001).

In addition, freshly obtained tumor samples had significantly lower TIL levels (P <.001), and in analysis of 20 paired primary and metastasis samples, there was a trend towards lower TIL levels in metastatic samples (P =.07).

“TIL levels were generally low at metastatic sites with the exception of lung metastases, which had significantly higher TIL levels (P <.001),” added Dr Luen.

After a median follow-up of 50 months for progression-free survival and 51 months for overall survival, results showed that there was no significant association between TIL values and progression-free survival (adjusted hazard ratio [HR], 0.95; 95% CI, 0.90-1.00; P =.063).

“There was a nonsignificant trend between higher TILs and improved progression-free survival and a significant association between higher TILs and improved overall survival,” said Dr Luen.

However, researchers found that each 10% increase in stromal TILs was significantly associated with an 11% reduction in the risk of death (adjusted HR, 0.89; 95% CI, 0.83-0.96; P =.0014). Dr Luen noted that this effect was linear.

“This is the first study investigating associations between TILs and survival in advanced HER2-positive breast cancer treated with first-line pertuzumab,” concluded Dr Luen. “The positive influence of pre-existing antitumor immunity persists in the advanced setting. Strategies to augment immunity may further improve survival.

Reference

1. Luen S, Salgado R, Stephen F, et al. Prognostic associations of tumor-infiltrating lymphocytes (TIL) in metastatic HER2-positive breast cancer (BC) treated with trastuzumab and pertuzumab: A secondary analysis of the CLEOPATRA study. Paper presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX.

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