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
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.