Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

e-Poster Display Session

103P - Temporospatial heterogeneity in metastatic colorectal cancer (mCRC)

Date

09 Dec 2020

Session

e-Poster Display Session

Presenters

Christos Fountzilas

Citation

Annals of Oncology (2020) 31 (suppl_7): S1457-S1458. 10.1016/annonc/annonc394

Authors

C. Fountzilas1, A. Witkiewicz2, J. Muhitch2, S. Abrams2, E. Knudsen2

Author affiliations

  • 1 Medicine, Roswell Park Comprehensive Cancer Center, 14263 - New York/US
  • 2 Roswell Park Comprehensive Cancer Center, Buffalo/US
More

Abstract 103P

Background

Anti-EGFR therapy has the potential to increase antitumor immune responses. Therapeutic strategies targeting EGFR and immune checkpoints may benefit patients (pts) with mCRC. We conducted a phase Ib/II clinical trial of cetuximab with pembrolizumab in RAS wild-type (RASwt) mCRC; the primary efficacy results of the trial have been reported (Fountzilas et al ESMO GI 2020). Herein, we present correlative tissue analysis.

Methods

Tumor biopsies were obtained baseline (pre-Tx) and after 12 weeks (post-Tx); multiplex immunohistochemistry for PD-L1, T-cell exhaustion (TIM3, CTLA4, LAG3) and activation (OX40) markers was performed. T-cells were characterized as partially activated-1 (OX40+/PD-L1-, 1/3 exhaustion markers+); partially activated-2 (OX40+/PD-L1-, 2/3 exhaustion markers+); partially activated-3 (OX40+/PD-L1-, 3/3 exhaustion markers+); exhausted-1 (OX40-/PD-L1-, 1/3 exhaustion markers+); exhausted-2 (OX40-/PD-L1-, 2/3 exhaustion markers+); and exhausted-3 (OX40-/PD-L1-, 3/3 exhaustion markers+).

Results

Forty-two pts were enrolled; 14 with matched pre-Tx and post-Tx biopsies, 24 with pre-Tx only. PD-L1 expression was higher in pre-Tx metastasis (M) vs. primary tumor (PT) in both tumor and stromal cells within the microenvironment (TME). The no. of activated T-cells was higher pre-Tx in PT compared to M. The no. of exhausted-2 T-cells in pre-Tx was higher in M vs. PT. The no. of activated T-cells and partially activated-1 T-cells was higher in post-Tx vs. pre-Tx M. There was no change in the no. of exhausted T-cells on post-Tx. PD-L1 decreased on tumor cells and increased in the TME on post-Tx.

Conclusions

Temporospatial heterogeneity in the immune landscape of the TME was evident in RASwt mCRC. With the limitation of small sample size, we observed increased PD-L1 expression and exhausted T-cells and decreased activated T-cells in M compared to PT. There was an increase in activated T-cells post-Tx, but the no. of exhausted T-cells was similar, potentially explaining the lack of additive benefit from pembrolizumab. Evaluating the PT in mCRC might not be reflective of immunosuppression in M. Combinations with mAb targeting other T-cell exhaustion pathways may be necessary to improve the antitumor efficacy of the EGFR-based regimens.

Clinical trial identification

NCT02713373.

Legal entity responsible for the study

Roswell Park Comprehensive Cancer Center.

Funding

Merck Sharp & Dohme Corp.

Disclosure

C. Fountzilas: Research grant/Funding (institution): Merck; Research grant/Funding (institution): National Comprehensive Cancer Network; Research grant/Funding (institution), free drug support: Pfizer. R. Iyer: Research grant/Funding (institution): Merck. All other authors have declared no conflicts of interest.

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
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.