1018O - Safety and Efficacy of Cisplatin Plus 5-Fu and Cetuximab in HPV-Positive and HPV-Negative Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN): Analysis of the Phase III Extreme Trial

Abstract

ABSTRACT Background Tumor human papillomavirus (HPV) status is a strong predictor of survival and response to treatment in patients (pts) with early and locally advanced oropharyngeal cancer, but its effects in R/M SCCHN remain to be clarified. This retrospective analysis of data from the EXTREME trial assessed the role of tumor HPV status in pts with R/M SCCHN receiving cisplatin + 5-FU chemotherapy (CT) alone or in combination with cetuximab. Material and methods: Immunohistochemical detection of p16INK4A was used to determine HPV status: p16-positive and p16-negative disease is referred to as HPV-positive (HPV+) and HPV-negative (HPV-) disease, respectively. Results 196/222 (88%) pts in the CT + cetuximab and 185/220 (84%) pts in the CT arm had tissue evaluable for p16. Of these, 91% and 88%, respectively, had HPV- tumors. Among HPV- pts, CT + cetuximab (n = 178) improved overall survival (OS), progression-free survival (PFS) and overall response rate (ORR), compared with CT (n = 162) (Table). A similar pattern was observed among HPV+ pts, between CT + cetuximab (n = 18) and CT (n = 23) for OS, PFS and ORR. Interaction tests between treatment and HPV status for OS and PFS confirmed that the treatment effect of CT + cetuximab vs CT was independent of tumor HPV status (p = 0.482 and p = 0.430, respectively: no significant interaction was noted). Within the CT + cetuximab and CT arms, HPV (p16) expression is associated with a more favorable outcome than HPV- (Table). In the CT + cetuximab arm, the overall incidence of grade 3/4 adverse events was slightly higher among HPV+ than HPV- pts. Conclusions Although the number of HPV+ pts in this analysis was low, the results suggest that in R/M SCCHN pts in the EXTREME trial, the survival benefits ofCT + cetuximab vs CT are independent of tumor HPV status and HPV (p16) expression is associated with a more favorable outcome than HPV-. Table: 1018O: Tumor HPV status: effects on prognosis and efficacy of CT + cetuximab and CT in R/M SCCHN. Population Comparison OS PFS ORR CT + cetuximab vs CT HPV- (n = 340) Median (months)/rate (%) 9.7 7.3 5.7 3.1 37 17 HR/odds ratio 95% CI p 0.822 (0.647–1.043) 0.1064 0.486 (0.376–0.628) 2.753 (1.655–4.579) HPV+ (n = 41) Median (months)/rate (%) 12.6 9.6 5.6 3.6 50 22 HR/odds ratio 95% CI p 0.628 (0.295–1.338) 0.2241 0.730 (0.363–1.469) 0.3761 3.600 (0.929–13.953) 0.0614 HPV+ vs HPV- CT + cetuximab (n = 196) Median (months)/rate (%) 12.6 9.7 5.6 5.7 50 37 HR/odds ratio 95% CI p 0.592 (0.319–1.098) 0.0925 1.172 (0.685–2.005) 0.5624 1.738 (0.657–4.600) 0.2620 CT (n = 185) Median (months)/rate (%) 9.6 7.3 3.6 3.1 22 17 HR/odds ratio 95% CI p 0.827 (0.504–1.355) 0.4492 0.871 (0.529–1.434) 0.5870 1.329 (0.455–3.880) 0.6025 Data are medians and hazard ratios (HR) for PFS and OS and rates and odds ratios for ORR. p: log-rank test for OS/PFS; Cochran-Mantel-Haenszel test for ORR. Disclosure B. De Blas: The author is an employee of Merck KGaA. I. Celik: The author is an employee of Merck KGaA J.B. Vermorken: I have participated in advisory boards of Merck-Serono, Amgen, Boehringer-Ingelheim, Genentech and Sanofi-aventis and have lectured (compensated) for Merck-Serono, Amgen, Bristol-Myers Squibb and Sanofi-aventis All other authors have declared no conflicts of interest.