Phase II prospective trial of induction chemotherapy for advanced sinonasal squamous cell or poorly differentiated carcinoma.
Authors: Contrera Kevin J. , Ferrarotto Renata , Gunn Gary Brandon , Su Shirley Y. , Kies Merrill S. , Glisson Bonnie S. , Garden Adam S. , Roberts Dianna , El-Naggar Adel K. , Williams Michelle D. , Raza Shaan , DeMonte Franco , Chen Melissa , Chambers Mark Steven , Hanna Ehab Y. 
Published: June 2023

6090 Background: The standard treatment for resectable advanced sinonasal carcinoma is surgery followed by adjuvant therapy. Despite aggressive therapy, disease control and survival have historically remained poor. The role of induction chemotherapy (IC) has not been fully assessed. The objective of this study is to prospectively evaluate IC for local disease control, organ preservation, and response-based local treatment selection. Methods: This is a phase II, open-label, single-center trial of patients with previously untreated, resectable and nonresectable, locally advanced squamous cell or poorly differentiated carcinoma of the nasal cavity or paranasal sinuses. Eligible patients were > 16 years of age, had an ECOG Performance Status of 0-1, and stage II-IV, M0 disease . Patients were treated with an IC regimen of docetaxel, cisplatin, and fluorouracil (TPF) for 2 cycles, then evaluated for response using clinical (symptoms and nasal endoscopy) and radiographic (RECIST 1.1 and PET) assessments. Those who achieved an objective response received a third cycle followed by chemoradiotherapy (CRT); non-responders underwent surgery with adjuvant radiotherapy. The primary endpoints were overall response rate (ORR) and 2-year local disease control. Secondary endpoints included disease-specific survival (DSS), overall survival (OS), disease-free survival (DFS), organ preservation, patterns of failure, and treatment toxicity. Results: 31 patients were enrolled between 2008 and 2020, of which 28 were evaluable for efficacy. Disease was T4a (57%) or T4b (21%), N+ (38%), and would have required maxillectomy (89%), craniotomy (54%), or orbital exenteration (29%). After IC, the ORR was 82.1% (7.1% complete response, 75.0% partial response), and the non-response rate was 17.9% (17.9% stable disease, 0% progressive disease). Patients then underwent CRT (79%) or surgery (21%). Following CRT, salvage surgery was performed for 41% of patients. Grade 3 or 4 adverse events occurred in 18% of patients. The 2-year local control rate was 53.6%. The 2-year DSS rate was 75% (median DSS not reached). For patients alive at 2 years, 63% had organ preservation (avoiding maxillectomy 38%, craniotomy 13%, orbital exenteration 38%). The median DFS and OS were 19.2 and 47.4 months, respectively. Factors associated with worse OS were nonwhite race ( P = .035), T4 category ( P = .037), overall stage IV ( P = .038), and paranasal sinus subsite ( P = .002). Surgery did not have significantly different OS than CRT ( P = .86). Conclusions: This phase II study demonstrates the validity of induction chemotherapy as a guide for local treatment selection in patients with advanced sinonasal carcinoma. A majority of patients achieved disease control and organ preservation. The median survival was 4 years in a cohort with very advanced locoregional disease, with no survival difference between CRT and surgery. NCT03493425. Clinical trial information: NCT00707473 .