Prognostic stratification of HPV-associated oropharyngeal cancer based on CD103+ immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomized trials

D Rischin; H Mehanna; R J Young; M Bressel; J Dunn; J Corry; P Soni; T Fulton-Lieuw; G Iqbal; L Kenny; S Porceddu; C Wratten; M Robinson; B J Solomon; Trans-Tasman Radiation Oncology Group and the De-ESCALaTE HPV Trial Group

doi:10.1016/j.annonc.2022.04.074

Prognostic stratification of HPV-associated oropharyngeal cancer based on CD103⁺ immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomized trials

Ann Oncol. 2022 Aug;33(8):804-813. doi: 10.1016/j.annonc.2022.04.074. Epub 2022 May 4.

Authors

Affiliations

¹ Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia. Electronic address: danny.rischin@petermac.org.
² Institute of Head and Neck Studies and Education (InHANSE), University of Birmingham, Birmingham, UK.
³ Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁴ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁵ Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.
⁶ Genesiscare St Vincent's Hospital, Melbourne, Australia; Department of Medicine, University of Melbourne, Melbourne, Australia.
⁷ Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁸ Department of Radiation Oncology, Royal Brisbane & Women's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia.
⁹ Faculty of Medicine, University of Queensland, Brisbane, Australia; Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Australia.
¹⁰ Department of Radiation Oncology, Calvary Mater Hospital and University of Newcastle, Newcastle, Australia.
¹¹ Cellular Pathology, Newcastle upon Tyne Hospitals, Newcastle, UK.
¹² Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia.

PMID: 35525376
DOI: 10.1016/j.annonc.2022.04.074

Abstract

Background: High CD103⁺ intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis.

Patients and methods: We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103⁺ ITIC high (≥30%) versus low (<30%). High and low CD103 were compared using Cox regression adjusting for age, stage and trial.

Results: Tumor samples were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. CD103⁺ ITIC abundance was high in 27% of patients. The median follow-up was 3.2 years. The 3-year FFS in patients treated with CETUX/RT was 93% [95% confidence interval (CI) 79% to 98%] in high CD103 and 74% (95% CI 63% to 81%) in low CD103 [adjusted hazard ratio = 0.22 (95% CI 0.12-0.41), P < 0.001]. The 3-year overall survival in patients treated with CETUX/RT was 100% in high CD103 and 86% (95% CI 76% to 92%) in low CD103, P < 0.001. In patients treated with CIS/RT, there was no significant difference in FFS.

Conclusions: CD103⁺ ITIC expression separates CETUX/RT-treated low-risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials.

Keywords: CD103; cetuximab; cisplatin; head and neck cancer; human papillomavirus; oropharyngeal cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cetuximab
Head and Neck Neoplasms* / complications
Humans
Oropharyngeal Neoplasms* / pathology
Papillomaviridae
Papillomavirus Infections* / complications
Prognosis
Randomized Controlled Trials as Topic

Substances

Cetuximab

Abstract

Publication types

MeSH terms

Substances

Grants and funding