PD-L1 Expression in Unresectable Locally Advanced or Metastatic Skin Squamous Cell Carcinoma Treated with Anti-Epidermal Growth Factor Receptor Agents

Stefano Cavalieri, Federica Perrone, Massimo Milione, Alba Bianco, Salvatore Alfieri, Laura D. Locati, Cristiana Bergamini, Carlo Resteghini, Donata Galbiati, Francesca Platini, Lisa Licitra, Paolo Bossi

Research output: Contribution to journalArticle

Abstract

Background: Recurrent or metastatic (R/M) skin squamous cell carcinoma (sSCC) not amenable of surgery or irradiation may benefit from systemic therapies. Epidermal growth factor receptor (EGFR) inhibitors and, more recently, immune checkpoint blockers (ICBs) showed activity in R/M sSCC. In this study, we aimed at exploring the possible role of PD-L1 expression in predicting response to anti-EGFR agents. Methods: Patients affected by R/M sSCC, treated with pan-HER inhibitor dacomitinib or with platinum-based chemotherapy with cetuximab (CT-cet) from 2010 to 2016, were considered. PD-L1 expression was assessed with immunohistochemistry on tumor cells (TCs) and on microenvironment (TC and tumor-infiltrating lymphocyte [IC] scores, respectively). Prognostic role of PD-L1 and the correlation with response to EGFR inhibitors and survival were analyzed. Results: Twenty-eight R/M sSCCs were analyzed (19 treated with dacomitinib, 9 with CT-cet). TC and IC were negative in 82 and 45% of cases, respectively; 15% sSCCs were both TC and IC positive. Progression-free survival (PFS) was longer in IC-positive cases (median 7.5 months vs. 2.1 in IC0, p = 0.02). No statistically significant differences were observed between PD-L1 expression and both overall survival and response rates. Conclusion: PD-L1 expression in microenvironment predicted better PFS. The combination of EGFR inhibitors and ICB could help deepening the knowledge about the interrelations between the EGFR and PD-1/PD-L1 pathways.

Original languageEnglish
Pages (from-to)112-118
Number of pages7
JournalOncology (Switzerland)
Volume97
Issue number2
DOIs
Publication statusPublished - Jul 1 2019

Fingerprint

Epidermal Growth Factor Receptor
Squamous Cell Carcinoma
Skin
Disease-Free Survival
Neoplasms
Tumor-Infiltrating Lymphocytes
Cellular Microenvironment
Drug Therapy
Platinum
Survival Rate
Immunohistochemistry
Survival
PF 00299804
Cetuximab
Therapeutics

Keywords

  • Anti-epidermal growth factor receptor treatment
  • Epidermal growth factor receptor
  • Outcome
  • PD-L1
  • Skin squamous cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

PD-L1 Expression in Unresectable Locally Advanced or Metastatic Skin Squamous Cell Carcinoma Treated with Anti-Epidermal Growth Factor Receptor Agents. / Cavalieri, Stefano; Perrone, Federica; Milione, Massimo; Bianco, Alba; Alfieri, Salvatore; Locati, Laura D.; Bergamini, Cristiana; Resteghini, Carlo; Galbiati, Donata; Platini, Francesca; Licitra, Lisa; Bossi, Paolo.

In: Oncology (Switzerland), Vol. 97, No. 2, 01.07.2019, p. 112-118.

Research output: Contribution to journalArticle

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title = "PD-L1 Expression in Unresectable Locally Advanced or Metastatic Skin Squamous Cell Carcinoma Treated with Anti-Epidermal Growth Factor Receptor Agents",
abstract = "Background: Recurrent or metastatic (R/M) skin squamous cell carcinoma (sSCC) not amenable of surgery or irradiation may benefit from systemic therapies. Epidermal growth factor receptor (EGFR) inhibitors and, more recently, immune checkpoint blockers (ICBs) showed activity in R/M sSCC. In this study, we aimed at exploring the possible role of PD-L1 expression in predicting response to anti-EGFR agents. Methods: Patients affected by R/M sSCC, treated with pan-HER inhibitor dacomitinib or with platinum-based chemotherapy with cetuximab (CT-cet) from 2010 to 2016, were considered. PD-L1 expression was assessed with immunohistochemistry on tumor cells (TCs) and on microenvironment (TC and tumor-infiltrating lymphocyte [IC] scores, respectively). Prognostic role of PD-L1 and the correlation with response to EGFR inhibitors and survival were analyzed. Results: Twenty-eight R/M sSCCs were analyzed (19 treated with dacomitinib, 9 with CT-cet). TC and IC were negative in 82 and 45{\%} of cases, respectively; 15{\%} sSCCs were both TC and IC positive. Progression-free survival (PFS) was longer in IC-positive cases (median 7.5 months vs. 2.1 in IC0, p = 0.02). No statistically significant differences were observed between PD-L1 expression and both overall survival and response rates. Conclusion: PD-L1 expression in microenvironment predicted better PFS. The combination of EGFR inhibitors and ICB could help deepening the knowledge about the interrelations between the EGFR and PD-1/PD-L1 pathways.",
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author = "Stefano Cavalieri and Federica Perrone and Massimo Milione and Alba Bianco and Salvatore Alfieri and Locati, {Laura D.} and Cristiana Bergamini and Carlo Resteghini and Donata Galbiati and Francesca Platini and Lisa Licitra and Paolo Bossi",
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T1 - PD-L1 Expression in Unresectable Locally Advanced or Metastatic Skin Squamous Cell Carcinoma Treated with Anti-Epidermal Growth Factor Receptor Agents

AU - Cavalieri, Stefano

AU - Perrone, Federica

AU - Milione, Massimo

AU - Bianco, Alba

AU - Alfieri, Salvatore

AU - Locati, Laura D.

AU - Bergamini, Cristiana

AU - Resteghini, Carlo

AU - Galbiati, Donata

AU - Platini, Francesca

AU - Licitra, Lisa

AU - Bossi, Paolo

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background: Recurrent or metastatic (R/M) skin squamous cell carcinoma (sSCC) not amenable of surgery or irradiation may benefit from systemic therapies. Epidermal growth factor receptor (EGFR) inhibitors and, more recently, immune checkpoint blockers (ICBs) showed activity in R/M sSCC. In this study, we aimed at exploring the possible role of PD-L1 expression in predicting response to anti-EGFR agents. Methods: Patients affected by R/M sSCC, treated with pan-HER inhibitor dacomitinib or with platinum-based chemotherapy with cetuximab (CT-cet) from 2010 to 2016, were considered. PD-L1 expression was assessed with immunohistochemistry on tumor cells (TCs) and on microenvironment (TC and tumor-infiltrating lymphocyte [IC] scores, respectively). Prognostic role of PD-L1 and the correlation with response to EGFR inhibitors and survival were analyzed. Results: Twenty-eight R/M sSCCs were analyzed (19 treated with dacomitinib, 9 with CT-cet). TC and IC were negative in 82 and 45% of cases, respectively; 15% sSCCs were both TC and IC positive. Progression-free survival (PFS) was longer in IC-positive cases (median 7.5 months vs. 2.1 in IC0, p = 0.02). No statistically significant differences were observed between PD-L1 expression and both overall survival and response rates. Conclusion: PD-L1 expression in microenvironment predicted better PFS. The combination of EGFR inhibitors and ICB could help deepening the knowledge about the interrelations between the EGFR and PD-1/PD-L1 pathways.

AB - Background: Recurrent or metastatic (R/M) skin squamous cell carcinoma (sSCC) not amenable of surgery or irradiation may benefit from systemic therapies. Epidermal growth factor receptor (EGFR) inhibitors and, more recently, immune checkpoint blockers (ICBs) showed activity in R/M sSCC. In this study, we aimed at exploring the possible role of PD-L1 expression in predicting response to anti-EGFR agents. Methods: Patients affected by R/M sSCC, treated with pan-HER inhibitor dacomitinib or with platinum-based chemotherapy with cetuximab (CT-cet) from 2010 to 2016, were considered. PD-L1 expression was assessed with immunohistochemistry on tumor cells (TCs) and on microenvironment (TC and tumor-infiltrating lymphocyte [IC] scores, respectively). Prognostic role of PD-L1 and the correlation with response to EGFR inhibitors and survival were analyzed. Results: Twenty-eight R/M sSCCs were analyzed (19 treated with dacomitinib, 9 with CT-cet). TC and IC were negative in 82 and 45% of cases, respectively; 15% sSCCs were both TC and IC positive. Progression-free survival (PFS) was longer in IC-positive cases (median 7.5 months vs. 2.1 in IC0, p = 0.02). No statistically significant differences were observed between PD-L1 expression and both overall survival and response rates. Conclusion: PD-L1 expression in microenvironment predicted better PFS. The combination of EGFR inhibitors and ICB could help deepening the knowledge about the interrelations between the EGFR and PD-1/PD-L1 pathways.

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KW - Epidermal growth factor receptor

KW - Outcome

KW - PD-L1

KW - Skin squamous cell carcinoma

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