FLYER

FLYER asked the de-escalation question that matters most to a 30-year-old: how little chemotherapy is enough. It enrolled people aged 18 to 60 with stage I or II aggressive B-cell non-Hodgkin lymphoma, a normal serum lactate dehydrogenase, performance status 0 or 1 and no bulky mass, at 138 sites in Germany, Denmark, Israel, Italy and Norway, and randomised them between six cycles of R-CHOP and four cycles of CHOP with six doses of rituximab.

At a median follow-up of 66 months, three-year progression-free survival with four cycles was 96 per cent (95 per cent confidence interval 94 to 99), 3 percentage points better than six cycles, which established non-inferiority against a margin of minus 5.5 points. The toxicity difference is the point of the trial: 294 haematological and 1,036 non-haematological adverse events in the four-cycle group against 426 and 1,280 in the six-cycle group. Two patients died during study therapy, both in the six-cycle group.

FLYER is why a young person with favourable limited-stage disease is now routinely offered four cycles rather than six, and why the conversation about radiotherapy in that setting is separate from the conversation about chemotherapy duration: no radiotherapy was planned in either arm except for testicular lymphoma.