Weakly cetuximab.

334 English, Irish and Dutch patients with low-risk oropharyngeal cancer enroll on a trial. No this isn’t the start to a bad joke, but the punchline ain't great. The De-ESCALaTE HPV trial included "low-risk" cases as defined by the RTOG 0129 risk stratification, i.e., HPV-positive with <10 pack-year histories. Important to note was the inclusion of any high-risk HPV subtype (not just HPV-16) based on FISH. They all received conventionally- fractionated definitive radiation to 70 Gy and were randomized to standard cisplatin every 3 weeks versus the “de-escalated” cetuximab weekly with a primary endpoint of grade ≥3 toxicity events at 2 years. Unfortunately the rate of toxicity was not improved, with each arm carrying a mean of 5 events per patient. More unfortunate was the secondary endpoint of rate of overall survival that was significantly worse with cetuximab (89%) versus cisplatin (98%). This appears driven by recurrence rates, which were 18% with cetuximab versus only 6% with cisplatin. Most remarkably, this was all in spite of the fact that less than 40% of patients in the cisplatin arm completed their planned course of systemic therapy compared to nearly 80% in the cetuximab arm. | Mehanna, Lancet 2018 (cetuximab saga part 1/2)

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