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...

Date 01 October 2012
Event ESMO Congress 2012
Session Head and neck cancer
Topics Anticancer Agents
Head and Neck Cancers
Biological Therapy
Presenter Amanda Psyrri
Authors A. Psyrri1, L. Licitra2, B. De Blas3, I. Celik4, J.B. Vermorken5
  • 1Internal Medicine, University of Athens Medical School, Attikon University Hospital, 12462 - Athens/GR
  • 2Oncologia Medica, Istituto Nazionale Tumori, Milan/IT
  • 3Global Clinical Development Unit Oncology, Merck KGaA, Darmstadt/DE
  • 4Global Research & Early Development, Merck KGaA, Darmstadt/DE
  • 5Department Of Medical Oncology, University Hospital Antwerp, Edegem/BE




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.


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.


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 of CT + 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) <0.0001 2.753 (1.655–4.579) <0.0001
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.


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.