Final report of a phase I trial of olaparib with cetuximab and radiation for heavy smoker patients with locally advanced head and neck cancer

Sana D. Karam, Krishna Reddy, Patrick J. Blatchford, Tim Waxweiler, Alicia M. DeLouize, Ayman Oweida, Hilary Somerset, Carrie Marshall, Christian Young, Kurtis D. Davies, Madeleine Kane, Aik Choo Tan, Xiao Jing Wang, Antonio Jimeno, Dara L. Aisner, Daniel W. Bowles, David Raben

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65 Citations (Scopus)


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 μg 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 μg orally twice daily, but the recommended phase II dose was deemed to be 25 μg 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, progressionfree 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 μg 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.

Original languageEnglish
Pages (from-to)4949-4959
Number of pages11
JournalClinical Cancer Research
Issue number20
Publication statusPublished - 2018 Oct 15

Bibliographical note

Funding Information:
Study drug only was provided by AstraZeneca. The company had no involvement in the study design or data interpretation. The authors thank the Wehling family for donations to support this clinical trial effort as well as the Marsico family for their endowment toward head and neck cancer research. This project was supported by Population Health Shared Resource, Molecular Pathology Shared Resource, and Genomics and Microarray Shared Resource, University of Colorado Cancer Center (P30CA046934).

Funding Information:
D.L. Aisner is a consultant/advisory board member for AbbVie and Genen-tech, and reports receiving commercial research grants from Genentech. No potential conflicts of interest were disclosed by the other authors.

Publisher Copyright:
© 2018 American Association for Cancer Research.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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