IMPAKT 2017: High Baseline TIL Levels Signal Superior Responses in HER2-Positive Breast Cancer

Significant association seen between high pretreatment TIL and pathological complete response following neoadjuvant chemotherapy plus anti-HER2 agents
04 May 2017

Baseline levels of tumour infiltrating lymphocytes (TIL) in pre-treatment biopsies from patients with HER2-positive breast cancer are significantly associated with pathological complete response (pCR) rates following neoadjuvant chemotherapy plus anti-HER2 agents (trastuzumab, lapatinib or their combination). These data, based on a meta-analysis of published data from five large clinical trials, will be reported at the IMPAKT Breast Cancer Conference in Brussels, Belgium on 4 to 6 May 2017.

Cinzia Solinas of the Institut Jules Bordet, Bruxelles, Belgium and colleagues performed a systematic search of the PubMed, Embase and Cochrane library databases for randomised controlled trials (RCT) investigating neoadjuvant chemotherapy plus trastuzumab, lapatinib or their combination in HER2-positive breast cancer up until 31 October, 2016. These investigators analyzed the relationship between the frequency of pCR and pre-treatment levels of TIL by comparing subgroups of patients with high baseline TIL or ‘other’ levels of TIL (non-high TIL).

This analysis included 1,256 patients participating in the CherLOB, GeparQuattro, GeparQuinto, GeparSixto and NeoALTTO neoadjuvant trials. Patients were stratified into TIL subgroups using the cut-off for high TIL defined in each study. The cut-off value for high TIL was 60% in the first four trials using trastuzumab, lapatinib or their combination plus anthracycline- and taxane-based neoadjuvant chemotherapy; whereas, in NeoALTTO the cut-off was 30% and the treatment regime was trastuzumab, lapatinib or their combination plus taxane only-based neoadjuvant chemotherapy.

High TIL levels were prognostic for pCR following neoadjuvant chemotherapy plus anti-HER2 agents

IMPAKT 2017 Abstract 27P

Association between TIL subgroups (high TIL versus non-high TIL) and pCR in the whole study population (any chemotherapy plus any anti-HER2 agent(s)).
Abbreviations: *: number of pathologic complete responses (pCR)/total number of patients in High TIL subgroup; +: number of pCR/total number of patients in non-high TIL subgroup; OR: odds ratio; CI: confidence interval; TIL: tumour-infiltrating lymphocytes; RE: random effect.
Credit: Cinzia Solinas

Evaluation of the data from all five trials using random and fixed effects models demonstrated a significant association between pCR rates and high pre-treatment levels of TIL with an odds ratio (OR) 2.46; 95% confidence interval (CI) 1.36, 4.43 (p = 0.003).

No interaction was observed between high versus non-high TIL subgroups in terms of response to anti-HER2 agents, trastuzumab versus lapatinib versus trastuzumab/lapatinib (p = 0.747) or between regimes containing anthracyclines plus taxanes versus taxanes alone (p = 0.201).

The association between pCR and high TIL was higher in the 869 patients participating in the CherLOB, GeparQuattro, GeparQuinto, GeparSixto trials of neoadjuvant anthracycline- and taxane-based chemotherapy, which employed a 60% cut-off to define high TIL, OR 2.88; 95% CI 2.03, 4.08 (p < 0.001).

Conclusions

The authors noted that in HER2-positive breast cancer, high baseline TIL are associated with increased pCR probability, irrespective of anti-HER2 agent(s) and neoadjuvant chemotherapy regimes used. The subgroup of patients with >60% TIL prior to treatment demonstrated a stronger benefit from neoadjuvant chemotherapy combined with anti-HER2 therapy.

Disclosure

Funding from the Belgian Fund for Scientific Research (FNRS), Les Amis de l’Institut Bordet, FNRS-Opération Télévie, Plan Cancer of Belgium was disclosed.

Reference

27P - C. Solinas, et al. Tumor infiltrating lymphocytes in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab, lapatinib or their combination: A meta-analysis of published randomized clinical trials

Last update: 04 May 2017

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings