ESMO 2019 — Controversy — Should therapy be de-escalated in patients with HPV+ oropharyngeal cancer?

  • Michael Simm
  • Oncology Conference reports
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  • Delegates voted twice on whether the time has come to de-escalate treatment in HPV+ oropharyngeal cancer (OPC) — at the beginning of a controversy session and after 2 experts had presented their views.


  • Both presenters agreed that positive clinical trials are required before de-escalation can be undertaken.
  • Hisham Mehanna was a self-confessed “de-escalationist” for 10 years. Based on 3 recent studies, he has now completely changed his mind.
  • In the first vote, 43.6% of delegates said we should de-escalate treatment for HPV+ OPC, while 29.5% said “No”.
  • In the second vote, opinions had changed with 21.8% voting “Yes” and 67.3% “No”.

Yes, treatment should be de-escalated — Christian Simon, Lausanne, Switzerland

  • The rates of late toxicity seen in pivotal trials have steadily increased over the last 25 years from approximately 18% to almost 50%.
  • Grade 3 toxicity for the oesophagus translates to liquids only, which may still result in pain on swallowing and may require dilation.
  • The death rate unrelated to cancer was 36% with chemoradiotherapy vs 18% with radiotherapy until 2012 (Forastiere et al. Journal of Clinical Oncology, 2013).
  • The incidence of aspiration pneumonia keeps increasing for at least 10 years after therapy and reaches 30%+ in patients over 75 years of age (Xu et al. Cancer, 2015).
  • Not having dysphagia is the second highest priority for patients (Ramaekers et al. Oral Oncology, 2011).
  • Qualifier: De-escalation is not for everyone and it should be done only once we have done the trials.

No, treatment should not be de-escalated — Hisham Mehanna, Birmingham, UK

  • The 3-year survival rate for low-risk HPV+ OPC is 93%, “and that rate comes at a cost.”
  • There are no alternative treatment regimes (to cisplatin and radiotherapy) with similar survival but less toxicity.
  • Patients want de-escalation only if there is no survival detriment. 37% would accept no reduction in survival at all. If the reduction of survival would be 5% or less for radiotherapy alone, 69% would rather choose chemoradiotherapy (Brotherston et al. Head Neck, 2012).
  • Replacing cisplatin with cetuximab did not work and resulted in worse overall survival. The absolute difference after 2 years was 23.8% (Mehanna et al. Lancet, 2018).
  • Just in are the results of phase 2 NRG-HN002 trial on p16-positive, non-smoking-associated, locoregionally advanced oropharyngeal cancer that failed to prove non-inferiority when radiotherapy was given without cisplatin (Yom S et al. ASTRO meeting 2019).