- 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).