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IMPAKT 2017: High Baseline Tumor-Infiltrating Lymphocyte Levels Signal Superior Responses in HER2-Positive Breast Cancer

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Key Points

  • Evaluation of the data from all five trials using random and fixed effects models demonstrated a significant association between pathologic complete response rates and high pretreatment levels of tumor-infiltrating lymphocytes.
  • No interaction was observed between high vs non-high TIL subgroups in terms of response to anti-HER2 agents, trastuzumab vs lapatinib vs trastuzumab/lapatinib or between regimens containing anthracyclines plus taxanes vs taxanes alone.
  • The association between pathologic complete response and high TIL levels was greater in the 869 patients participating in the CherLOB, GeparQuattro, GeparQuinto, and GeparSixto trials of neoadjuvant anthracycline- and taxane-based chemotherapy.

Baseline levels of tumor-infiltrating lymphocytes (TILs) in pretreatment biopsies from patients with HER2-positive breast cancer are significantly associated with pathologic complete response rates following neoadjuvant chemotherapy plus anti-HER2 agents (trastuzumab [Herceptin], lapatinib [Tykerb], or their combination). These data, based on a meta-analysis of published data from five large clinical trials, were reported by Solinas et al at the 2017 IMPAKT Breast Cancer Conference in Brussels (Abstract 27P). The IMPAKT conference is a collaborative effort by the European Society for Medical Oncology, the Breast International Group, and a multidisciplinary alliance of other European breast cancer organizations.

Background

Cinzia Solinas, MD, of the Institut Jules Bordet in Brussels, and colleagues performed a systematic search of the PubMed, Embase, and Cochrane library databases for randomized controlled trials investigating neoadjuvant chemotherapy plus trastuzumab, lapatinib, or their combination in HER2-positive breast cancer up until October 31, 2016. The investigators analyzed the relationship between the frequency of pathologic complete response and pretreatment levels of TILs by comparing subgroups of patients with high baseline TILs or “other” levels of TILs (“non-high TILs”).

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 cutoff for high TIL levels defined in each study. The cutoff value for high TILs was 60% in the first four trials using trastuzumab, lapatinib, or their combination plus anthracycline- and taxane-based neoadjuvant chemotherapy, whereas, in NeoALTTO, the cutoff was 30% and the treatment regimen was trastuzumab, lapatinib, or their combination plus taxane only–based neoadjuvant chemotherapy.

Study Findings

Evaluation of the data from all five trials using random and fixed effects models demonstrated a significant association between pathologic complete response rates and high pretreatment levels of TILs (odds ratio [OR] = 2.46, 95% confidence interval [CI] = 1.36–4.43, P = .003).

No interaction was observed between high vs non-high TIL subgroups in terms of response to anti-HER2 agents, trastuzumab vs lapatinib vs trastuzumab/lapatinib (P = .747), or between regimens containing anthracyclines plus taxanes vs taxanes alone (P = .201).

The association between pathologic complete response and high TILs was greater in the 869 patients participating in the CherLOB, GeparQuattro, GeparQuinto, and GeparSixto trials of neoadjuvant anthracycline- and taxane-based chemotherapy, which employed a 60% cutoff to define high TILs (OR = 2.88, 95% CI = 2.03–4.08, P < .001).

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

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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