TY - JOUR
T1 - E1308
T2 - Phase II trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx- ECOG-ACRIN cancer research group
AU - Marur, Shanthi
AU - Li, Shuli
AU - Cmelak, Anthony J.
AU - Gillison, Maura L.
AU - Zhao, Weiqiang J.
AU - Ferris, Robert L.
AU - Westra, William H.
AU - Gilbert, Jill
AU - Bauman, Julie E.
AU - Wagner, Lynne I.
AU - Trevarthen, David R.
AU - Balkrishna, Jahagirdar
AU - Murphy, Barbara A.
AU - Agrawal, Nishant
AU - Colevas, A. Dimitrios
AU - Chung, Christine H.
AU - Burtness, Barbara
N1 - Funding Information: This study was coordinated by the ECOG-ACRIN Cancer Research Group and supported in part by US Public Health Service Grant Nos. CA180794, CA180820, CA180802, CA180847, CA180844, CA189805, CA180816, CA189863, CA180826, and CA189856; and by the National Cancer Institute, National Institutes of Health, and the US Department of Health and Human Services. Publisher Copyright: © 2016 by American Society of Clinical Oncology.
PY - 2017/2/10
Y1 - 2017/2/10
N2 - Purpose: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is treatment-responsive. Definitive chemoradiation results in high cure rates but causes long-term toxicity and may represent overtreatment of some patients. This phase II trial evaluated whether complete clinical response (cCR) to induction chemotherapy (IC) could select patients with HPV-associated OPSCC for reduced radiation dose as a means of sparing late sequelae. Methods: Patients with HPV16 and/or p16-positive, stage III-IV OPSCC received three cycles of IC with cisplatin, paclitaxel, and cetuximab. Patients with primary-site cCR to IC received intensity-modulated radiation therapy (IMRT) 54 Gy with weekly cetuximab; those with less than cCR to IC at the primary site or nodes received 69.3 Gy and cetuximab to those regions. The primary end point was 2-year progression-free survival. Results: Of the 90 patients enrolled, 80 were evaluable. Their median age was 57 years (range, 35 to 73 years), with the majority having stage T1-3N0-N2b OPSCC and a history of ≤ 10 pack-years of cigarette smoking. Three cycles of IC were delivered to 77 of the 80 patients. Fifty-six patients (70%) achieved a primary-site cCR to IC and 51 patients continued to cetuximab with IMRT 54 Gy. After median follow-up of 35.4 months, 2-year progression-free survival and overall survival rates were 80% and 94%, respectively, for patients with primary-site cCR treated with 54 Gy of radiation (n = 51); 96% and 96%, respectively, for patients with < T4, < N2c, and ≤ 10 pack-year smoking history who were treated with ≤ 54 Gy of radiation (n = 27). At 12 months, significantly fewer patients treated with a radiation dose ≤ 54 Gy had difficulty swallowing solids (40% v 89%; P = .011) or had impaired nutrition (10% v 44%; P = .025). Conclusion: For IC responders, reduced-dose IMRT with concurrent cetuximab is worthy of further study in favorable-risk patients with HPV-associated OPSCC. Radiation dose reduction resulted in significantly improved swallowing and nutritional status.
AB - Purpose: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is treatment-responsive. Definitive chemoradiation results in high cure rates but causes long-term toxicity and may represent overtreatment of some patients. This phase II trial evaluated whether complete clinical response (cCR) to induction chemotherapy (IC) could select patients with HPV-associated OPSCC for reduced radiation dose as a means of sparing late sequelae. Methods: Patients with HPV16 and/or p16-positive, stage III-IV OPSCC received three cycles of IC with cisplatin, paclitaxel, and cetuximab. Patients with primary-site cCR to IC received intensity-modulated radiation therapy (IMRT) 54 Gy with weekly cetuximab; those with less than cCR to IC at the primary site or nodes received 69.3 Gy and cetuximab to those regions. The primary end point was 2-year progression-free survival. Results: Of the 90 patients enrolled, 80 were evaluable. Their median age was 57 years (range, 35 to 73 years), with the majority having stage T1-3N0-N2b OPSCC and a history of ≤ 10 pack-years of cigarette smoking. Three cycles of IC were delivered to 77 of the 80 patients. Fifty-six patients (70%) achieved a primary-site cCR to IC and 51 patients continued to cetuximab with IMRT 54 Gy. After median follow-up of 35.4 months, 2-year progression-free survival and overall survival rates were 80% and 94%, respectively, for patients with primary-site cCR treated with 54 Gy of radiation (n = 51); 96% and 96%, respectively, for patients with < T4, < N2c, and ≤ 10 pack-year smoking history who were treated with ≤ 54 Gy of radiation (n = 27). At 12 months, significantly fewer patients treated with a radiation dose ≤ 54 Gy had difficulty swallowing solids (40% v 89%; P = .011) or had impaired nutrition (10% v 44%; P = .025). Conclusion: For IC responders, reduced-dose IMRT with concurrent cetuximab is worthy of further study in favorable-risk patients with HPV-associated OPSCC. Radiation dose reduction resulted in significantly improved swallowing and nutritional status.
UR - http://www.scopus.com/inward/record.url?scp=85012216644&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85012216644&partnerID=8YFLogxK
U2 - 10.1200/JCO.2016.68.3300
DO - 10.1200/JCO.2016.68.3300
M3 - Article
C2 - 28029303
SN - 0732-183X
VL - 35
SP - 490
EP - 497
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 5
ER -