A higher quantity of stromal tumor-infiltrating lymphocytes (TILs) was associated with better overall survival in patients with advanced HER2-positive breast cancer treated with either pertuzumab or placebo, along with trastuzumab and docetaxel, according to a new study.
“Data from many studies in HER2-positive early breast cancer have shown associations between higher quantities of TILs” and positive treatment outcomes, wrote study authors led by Sherene Loi, MD, PhD, of Peter MacCallum Cancer Centre at the University of Melbourne in Australia. That association between TILs and prognosis was not previously known in the advanced setting.
The new study was an analysis of 678 patients out of 808 included in the CLEOPATRA trial, which compared pertuzumab to placebo along with trastuzumab and docetaxel in women with locally recurrent, unresectable, or metastatic HER2-positive breast cancer. TIL levels were assessed and correlated with survival outcomes; the results were published online ahead of print in Lancet Oncology.
The mean stromal TIL value was 21.07%, and the median value was 10%. On a univariate analysis, the hazard ratio (HR) for progression-free survival for each 10% increment increase in TILs was 0.97 (95% CI, 0.93–1.11; P = .15). There was a significant correlation, however, for overall survival, with an HR of 0.93 (95% CI, 0.89–0.98; P = .011).
These results remained similar on a multivariate analysis, with an HR for progression-free survival associated with each 10% TIL increment of 0.95 (95% CI, 0.90–1.00; P = .063); for overall survival, the HR was 0.89 (95% CI, 0.83–0.96; P = .0014).
The treatment effect of pertuzumab did not differ significantly according to stromal TIL value with regard to either progression-free or overall survival. The 3-year overall survival rate was 50% in placebo-treated patients with stromal TIL values of 20% or less, compared with 55% in those with TIL values above 20%. For the pertuzumab group, these rates were 64% and 78%, respectively.
The authors noted that they found lower TIL values in metastatic tumor samples than in paired primary samples, but there were too few of these paired samples to power a statistical analysis.
“Our data suggest that the positive prognostic effect of antitumor immunity persists in the advanced setting and that freshly obtained biopsy samples will be informative for the assessment of pre-existing antitumor immunity,” the authors wrote. “Our data also suggest that the TIL biomarker should be considered as a stratification parameter in future clinical trials.”