14P - The effector capacity of peripheral blood mononuclear cells (PBMCs) from HER2+ breast cancer (BC) patients treated with chemotherapy and HER2-targe...

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Nicola Gaynor
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors N. Gaynor1, A. Canonici1, A. Eustace2, M. McDermott3, N. O'Donovan3, J. Crown4, D.M. Collins3
  • 1National Institute For Cellular Biotechnology, Dublin City University, Dublin 9 - Dublin/IE
  • 2Rcsi Education & Research Centre, Royal College of Surgeons in Ireland, Dublin/IE
  • 3National Institute For Cellular Biotechnology, Dublin City University, Dublin/IE
  • 4St Vincents University Hospital, St Vincents University Hospital, 4 - Dublin/IE

Abstract

Aim/Background

The phase II neoadjuvant clinical trial ICORG10-05 compared chemotherapy (docetaxel, carboplatin - DC) in combination with trastuzumab (T), trastuzumab and lapatinib (L) or L alone in HER2+ BC patients. T is a monoclonal antibody (mAb) which targets the extracellular portion of HER2, inhibiting intracellular signalling pathways and eliciting antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by immune effector cells. L is a dual HER2/EGFR tyrosine kinase inhibitor. Pre- and post-treatment (pre-surgery) PBMCs were examined for their ability to elicit direct PBMC-mediated cytotoxicity (DPMC) and T-mediated ADCC (T-ADCC) with results examined by treatment arm and patient response.

Methods

Blood samples were processed within 4 hours of being drawn. PBMCs were isolated by density centrifugation and frozen. 24 matched pre- and post-treatment samples from DCTL (n = 10), DCT (n = 8), DCL (n = 6) were included in analysis. Revived PBMCs were assessed for viability (average +/- std. dev. = 78.9 +/- 23.6%). Using a flow cytometry-based method, DPMC was measured against the non-MHC-restricted leukemic cell line K562 and T-ADCC measured against HER2+ BC cell line SKBR3. Assays were conducted over 4 hours at a PBMC: target cell ratio of 10:1. The mAb rituximab was used as an ADCC negative control.

Results

Overall, post-treatment samples (n = 24) showed reduced DPMC against K562 (p = 0.034) and reduced T-ADCC against SKBR3 (p = 0.026) compared to pre-treatment levels. There was no significant difference in DPMC between treatment arms, pre- or post-treatment. There were significantly higher levels of DPMC against K562 for partial responders (PR) than complete responders (CR) post-treatment (p = 0.006). Post-treatment levels of T-ADCC against SKBR3 were greater in PR than CR patients but did not reach statistical significance (p = 0.078).

Conclusions

Our results suggest that chemotherapy used in ICORG 10-05 reduces the effector activity of circulating PBMCs with no difference between T, L or TL in combination with DC. Our data indicates further work examining PBMC cytotoxicity by patient response cohort is warranted.

Clinical trial identification

NCT01485926, trial ongoing, primary completion date September 2014.

Legal entity responsible for the study

Cancer Trials Ireland (Formerly the All Ireland Clinical Oncology Research Group)

Funding

Cancer Clinical Research Trust, GSK

Disclosure

N. O\'Donovan: Received research funding from GSK and Roche. J. Crown: Consulting fees for AdBoards: Novartis, Eisai, Pfizer, Genomic Health, Bayer, Teva, Amgen, Vertex, Boehringer Ingelheim, NEO New Oncology, Seattle Genetics Research funding: Roche, GSK, Eisai, Boehringer Ingelheim. D.M. Collins: Received research funding from Roche Diagnostics GmbH as part of a Roche Postdoctoral Fellowship. All other authors have declared no conflicts of interest.