The modified-intensity groups came out noninferior for the primary endpoint of 5-year freedom from treatment failure compared with the usual eight-cycle escalated BEACOPP regimen.

Results were similar for progression-free survival.

But a post-hoc analysis of time to progression suggested the 2-week cycle regimen wasn’t as effective as the six-cycle regimen, with a 5-year time to progression of 87.7% versus 92.6% with eight cycles (P=0.016).

The shorter cycles also didn’t improve overall survival.

The lower mortality rate with the six-cycle group - at 4.6% versus 5.2% with the shorter eight-cycle regimen and 7.5% with the longer eight-cycle regimen - appeared to be mainly due to fewer treatment-related events and secondary cancers.

Anemia rates were similar between groups, but the group given eight cycles every two weeks had somewhat less leukopenia (70% versus about 90% in both other groups) and 2 to 3 times less thrombocytopenia.

On the other hand, neurotoxic effects and pulmonary toxic effects occurred more frequently with the accelerated-dosing group.

Overall, “the therapy-related death rate reported with six cycles of escalated BEACOPP compared favourably with ABVD at less than 1%,” the commentary pointed out.

Secondary malignancies occurred at a rate of 3.4% overall, similar to the roughly 3% rate previously reported for ABVD, the researchers noted.

The secondary cancer rate was higher, though, in the eight-cycle group on a 3-week schedule compared with the six-cycle group (P=0.02).

The number of secondary acute myeloid leukemias or myelodysplastic syndromes was lowest - at two - with the six-cycle group, eight with the eight-cycle regimen every 2 weeks, and 19 for the other eight-cycle group (P=0.0001 versus six cycles).

Fewer patients receiving additional radiotherapy due to PET scan guidance - just 11% compared with over 70% in a prior trial with escalated BEACOPP - would also be expected to result in fewer second solid tumors, the researchers noted.

The negative predictive value for PET at 12 months was 94.1%, supporting it as a prognostic tool in determining therapy, the group added.

Casasnovas and Coiffier suggested that a PET scan after the first two cycles of therapy could be useful or identifying candidates for de-escalation to ABVD, although further research will be needed to figure out which patients need less than six cycles of escalated BEACOPP.

Primary source: The Lancet
Source reference: Engert A, et al “Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial” Lancet 2012; DOI: 10.1016/S0140-6736(11)61940-5.

Additional source: The Lancet
Source reference: Casasnovas O, Coiffier B “Escalated BEACOPP in advanced Hodgkin’s lymphoma” Lancet 2012; DOI: 10.1016/S0140-6736(12)60153-6.