E1308: 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

Abstract

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 HPVassociated OPSCC for reduced radiation dose as a means of sparing late sequelae. MethodsPatients 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 intensitymodulated 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. ResultsOf 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). ConclusionFor 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.

NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017

“…42,43,50 The ECOG-ACRIN phase II E1308 trial, in which patients with stage III-IV HPV16 and/or p16-positive oropharyngeal cancer (N=80) received induction chemotherapy followed by reduced-dose RT and weekly cetuximab, recently reported results showing that RT deintensification may result in equivalent or similar responses in selected patients compared with fulldose RT. 51 The relationship between HPV and other prognostic or predictive factors such as smoking history and stage has been investigated. 52,53 For example, analyses of patients with oropharyngeal cancer who were enrolled in RTOG 9003 or 0129 (n=165) showed that smoking was associated with decreased OS and PFS, regardless of p16 status.…”

Premature Discontinuation of Curative Radiation Therapy: Insights from Head and Neck Irradiation

“…The 2-year overall survival with a total dose of 54 Gy and concurrent cetuximab was 94%. 19 The current study has several important limitations. A short follow-up and small sample size prevented us from making conclusions with regard to the effect of PDCRT on long-term clinical outcomes.…”

Response to R-CHOP in HPV-related squamous cell carcinoma of base of tongue: a case report

“…In a prospective trial of lowrisk HPV + patients (T1-3 N0-N2b), 3 cycles of induction chemotherapy with cisplatin, paclitaxel, and cetuximab achieved an excellent complete clinical response (cCR) rate of 70%, which subsequently enabled them to be treated with a substantially lower dose of radiation (54Gy vs. 69. 3Gy) [36]. In fact, the benefit of chemotherapy is unclear in this selected group of low-risk patients and efforts are underway to evaluate if chemotherapy can be omitted altogether ( [35] and clinical trial NCT02254278).…”