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

Ann Oncol. 2019 Feb 1;30(2):297-302. doi: 10.1093/annonc/mdy522.


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.

Keywords: chemoradiation; human papillomavirus; induction chemotherapy; oropharyngeal cancer; treatment de-escalation.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Carcinoma, Squamous Cell / virology
  • Cetuximab / administration & dosage
  • Chemoradiotherapy / mortality*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / therapy*
  • Oropharyngeal Neoplasms / virology
  • Paclitaxel / administration & dosage
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology
  • Prognosis
  • Survival Rate


  • Carboplatin
  • Paclitaxel
  • Cetuximab

Associated data

  • ClinicalTrials.gov/NCT02258659