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

• Published in: Annals of oncology Vol. 33; no. 8; pp. 804 - 813
• Main Authors: Rischin, D, Mehanna, H, Young, R J, Bressel, M, Dunn, J, Corry, J, Soni, P, Fulton-Lieuw, T, Iqbal, G, Kenny, L, Porceddu, S, Wratten, C, Robinson, M, Solomon, B J
• Format: Journal Article
• Language: English
• Published: England 01-08-2022
• Subjects: Cetuximab; Head and Neck Neoplasms - complications; Humans; Oropharyngeal Neoplasms - pathology; Papillomaviridae; Papillomavirus Infections - complications; Prognosis; Randomized Controlled Trials as Topic; cetuximab; oropharyngeal cancer; head and neck cancer; CD103; cisplatin; human papillomavirus
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1016/j.annonc.2022.04.074

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.
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.
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.
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.