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Multi-institution Analysis of Concurrent Chemoradiation Therapy With Cisplatin (CDDP) Versus Cetuximab (C225) in Locally-Advanced Squamous Cell Carcinoma of the Head and Neck (LA-HNSCC): Can HPV Help Decide Which Agent?
N. Riaz,1 A. Baschnagel,2 D. Adkins,3 S. Rao,1 J. Huang,3 P. Chen,2 J. Ley,3 D. Krauss,2 W. Thorstad,3 and N. Lee1; 1Memorial Sloan- Kettering Cancer Center, New York, NY, 2Beaumont Hospital, Royal Oak, MI, 3Washington University, St Louis, MO
Purpose/Objective(s): Multiple institutions have reported that patients with LA-HNSCC treated with concurrent C225-based radiation therapy (RT) have worse outcomes than those treated with concurrent CDDP. HPV’s influence on the treatment efficacy of these two agents is unclear. In the metastatic setting, HPV patients treated with Panitumumab had improved overall survival (OS), while no difference was found in HPV+ patients. We sought to investigate whether the previously reported differences in outcomes in LA-HNSCC between C225 and CDDP were influenced by HPV Status.
Materials/Methods: We reviewed the records of 147 consecutive patients with LA-HNSCC treated with definitive chemo-RT at one of our 3 institutions with known HPV status. Patients with nasopharyngeal carcinoma, oral cavity carcinoma, or distant metastasis at time of presentation were excluded. Further, patients who received induction chemotherapy or additional concurrent systemic agents were excluded. At institution 1,
HPV Status was determined by p16 or HPV ISH; at institute 2 by PCR or p16; and at institute 3 by p16 or non-keratinizing histology. Smoking status was divided between those with a 10 pack-yr history or greater vs those without. Actuarial curves were created with the Kaplan-Meier method and multivariate Analysis (MVA) was performed with a Cox-regression model.
Results: Median follow-up in surviving patients was 43 months. Ninetytwo (63%) patients were treated with CDDP and 55 (37%) with C225.
T-stage, N-stage, smoking, and alcohol consumption were well balanced between the two groups. There were more patients greater than 70 yrs of age in the C225 group (22% vs 6%, p < 0.001) and more HPV- patients (44% vs 25%, p Z 0.03). The 2-year cumulative incidence of locoregional failure (LRF) was significantly higher with C225 compared to CDDP (41.9% vs 12.6%, p < 0.001). Subgroup analysis of patients by
HPV status revealed increased 2-yr LRF with C225 in HPV+ patients (33.6% vs 10.4%, p Z 0.02) and in HPV- patients (52.6% vs 20.3%, p Z
0.02). MVA of LRF adjusting for HPV, T Stage, and N Stage continued to show improved outcomes with CDDP (HR Z 0.26, p Z 0.002). The
2-year DFS was also significantly worse with C225 compared to CDDP (38.6% vs 82.6%, p < 0.001). Subgroup analysis by HPV again revealed
worse 2-yr DFS with C225 in HPV+ (46.4% vs 84.8%, p < 0.001) and HPV- patients (29.2 vs 74.9%, p < 0.001). MVA of DFS adjusting for
HPV, Age, T stage, N Stage, and smoking demonstrated improved DFS with CDDP (HR Z 0.31, p < 0.001). Results for OS were similar.
Conclusions: Loco-regional control and DFS are significantly improved with concurrent cisplatin as compared to cetuximab in definitive RT for
HNSCC. Both HPV+ and HPV patients benefit from CDDP-based concurrent therapy in LA-HNSCC
Marur : Schéma thérapeutique qui semble réalisable Mais faible recul : 12 mois
Sélection par la chimiothérapie ou par le statut HPV?