Optima: A phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer

T. Y. Seiwert, C. C. Foster, E. A. Blair, T. G. Karrison, N. Agrawal, J. M. Melotek, L. Portugal, R. J. Brisson, A. Dekker, S. Kochanny, Z. Gooi, M. W. Lingen, V. M. Villaflor, D. T. Ginat, D. J. Haraf, E. E. Vokes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background Patients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy. Patients and methods Patients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%-50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity. Results Sixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001). Conclusions Induction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified. Clinical trial registration Clinical trials.gov identifier: NCT02258659.

Original languageEnglish (US)
Pages (from-to)297-302
Number of pages6
JournalAnnals of Oncology
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2019

Keywords

  • Chemoradiation
  • Human papillomavirus
  • Induction chemotherapy
  • Oropharyngeal cancer
  • Treatment de-escalation

ASJC Scopus subject areas

  • Hematology
  • Oncology

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