Final Report of a Phase I Trial of Olaparib with Cetuximab and Radiation for Heavy Smoker Patients with Locally Advanced Head and Neck Cancer

Clin Cancer Res. 2018 Oct 15;24(20):4949-4959. doi: 10.1158/1078-0432.CCR-18-0467. Epub 2018 Jul 3.


Purpose: Our goal was to evaluate the safety and toxicity of combining a PARP inhibitor, olaparib, with cetuximab and fractionated intensity-modulated radiotherapy for patients with locally advanced head and neck cancer and heavy smoking histories.Patients and Methods: Patients with ≥10 packs/year history of smoking were treated with olaparib at doses ranging from 25-200 mg orally twice daily beginning approximately 10 days prior to initiation of and with concurrent radiation (69.3 Gy in 33 fractions) using a time-to-event continual reassessment method model. Cetuximab was administered starting approximately 5 days prior to radiation per standard of care.Results: A total of 16 patients were entered onto the study, with 15 evaluable for acute toxicity. The most common treatment-related grade 3-4 side effects were radiation dermatitis and mucositis (38% and 69%, respectively). The MTD was determined to be 50 mg orally twice daily, but the recommended phase II dose was deemed to be 25 mg orally twice daily. At a median follow-up of 26 months, the actuarial median overall survival was 37 months, but was not reached for other endpoints. Two-year overall survival, progression-free survival, local control, and distant control rates were 72%, 63%, 72%, and 79%, respectively. Patients who continued to smoke during therapy experienced higher recurrence rates. MYC and KMT2A were identified as potential correlatives of response on gene amplification and mutational analysis.Conclusions: Olaparib at 25 mg orally twice daily with concurrent cetuximab and radiation was well tolerated with reduced dermatitis within the radiation field. Response rates were promising for this high-risk population. Clin Cancer Res; 24(20); 4949-59. ©2018 AACR.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Cetuximab / administration & dosage
  • Combined Modality Therapy
  • DNA Mutational Analysis
  • Female
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Phthalazines / administration & dosage
  • Piperazines / administration & dosage
  • Prognosis
  • Radiotherapy, Image-Guided
  • Radiotherapy, Intensity-Modulated*
  • Smokers*
  • Transcriptome
  • Treatment Outcome


  • Biomarkers, Tumor
  • Phthalazines
  • Piperazines
  • Cetuximab
  • olaparib