High Stromal TILs Linked To Improved OS In Advanced HER2-Positive Breast Cancer

Tumour infiltrating lymphocyte levels could serve as a prognostic marker in women with locally advanced or metastatic HER2-positive breast cancer

medwireNews: Among patients with advanced HER2-positive breast cancer treated with docetaxel plus trastuzumab alongside either pertuzumab or placebo, high levels of stromal tumour infiltrating lymphocytes (TILs) are associated with prolonged overall, but not progression-free, survival, indicates a secondary analysis of the CLEOPATRA trial.

These findings extend “the prognostic role of TILs outside the primary disease setting”, say the study authors, adding that: “Future clinical studies in this cancer subtype should consider TILs as a stratification factor and investigate whether therapies that can augment immunity could potentially further improve survival.”

The phase III trial, in which women with locally recurrent, unresectable or metastatic breast cancer were randomly assigned to receive either pertuzumab or placebo alongside docetaxel and trastuzumab, previously showed that pertuzumab addition significantly improved overall survival (OS).

In the current analysis, which included 678 patients with sufficient tumour tissue for TIL testing (84.0% of 808 trial participants), the average stromal TIL value was 21.1% whereas the median was 10.0%.

Median OS was longer for participants with TIL levels over 20% than for those with levels at or below this cutoff, at 56.6 and 44.5 months, respectively.

And multivariate analysis adjusting for confounders, such as age, ethnicity and oestrogen receptor status, showed that each 10% increase in stromal TIL levels significantly reduced the risk of death by 11%.

However, TIL levels were not significantly associated with progression-free survival (PFS), report Sherene Loi, from the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia, and co-workers in The Lancet Oncology.

Moreover, they found that the “treatment effect of pertuzumab did not differ significantly by stromal TIL value” for either survival outcome – that is, patients who received pertuzumab had better OS and PFS than their placebo-treated counterparts, regardless of the TIL levels.

In a related commentary, Arlene Chan, from Curtin University in Nedlands, Western Australia, says that “[t]hese findings reaffirm the important part that host immunity plays in terms of outcomes in patients receiving anti-HER2 treatment.”

She continues: “However, the discordance between the results for overall survival and progression-free survival in the current study could suggest that the tumour immune environment remains important in response to subsequent therapies given after progression on trastuzumab–pertuzumab-based treatment.”

References

Luen SJ, Salgado R, Fox S, et al. Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study. Lancet Oncol; Advance online publication 7 December 2016. doi: http://dx.doi.org/10.1016/S1470-2045(16)30631-3

Chan A. TILs in metastatic breast cancer—no surprises, but more questions. Lancet Oncol; Advance online publication 7 December 2016. doi: http://dx.doi.org/10.1016/S1470-2045(16)30637-4

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