HD18
PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group
Phase 3N = 2,101NCT00515554
- Population
- Newly diagnosed advanced-stage Hodgkin's lymphoma, aged 18 to 60 years, recruited between May 2008 and July 2014 in Germany, Switzerland, Austria, the Netherlands and the Czech Republic; 2101 patients recruited, of whom 137 were ineligible before randomisation and a further 19 after randomisation.
- Design
- Open-label, international, randomised phase 3 trial. After central review of the PET result after two cycles of eBEACOPP (PET-2), patients were assigned to one of two parallel treatment groups. PET-2-positive patients (434 randomised, 217 per arm) were randomised to eBEACOPP alone or eBEACOPP with rituximab (8 cycles in total). PET-2-negative patients were randomised to standard eBEACOPP (8 cycles; 6 cycles after a protocol amendment in June 2011) or to 4 cycles of eBEACOPP in total. Primary endpoint progression-free survival; the aims were superiority of the experimental treatment in the PET-2-positive cohort and non-inferiority (absolute difference of 6% in 5-year PFS) in the PET-2-negative cohort. Primary analyses in the PET-2-negative cohort were per protocol; all other analyses were by intention to treat. After the June 2011 amendment, PET-2-positive patients were no longer randomised and all received 6 cycles of eBEACOPP.
- Primary endpoint
- PFS
- Arms
- PET-2-positive: eBEACOPP (control, n = 217): Eight cycles of eBEACOPP in total (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, escalated doses)
- PET-2-positive: R-eBEACOPP (experimental, n = 217): Eight cycles of eBEACOPP in total with rituximab 375 mg/m2 (maximum total dose 700 mg)
- PET-2-negative: standard eBEACOPP (control, n = 504): Eight cycles of eBEACOPP in total (six cycles after the June 2011 protocol amendment)
- PET-2-negative: 4 cycles of eBEACOPP (experimental, n = 501): Two additional cycles after PET-2, four cycles of eBEACOPP in total
- People
- Borchmann P, senior author Engert A, German Hodgkin Study Group
Δ 60-month PFS+1.4 pointsΔ 60-month PFS−1.6 points
Show the numbers
| Endpoint | Analysis | PET-2-positive: R-eBEACOPP / PET-2-negative: 4 cycles of eBEACOPP | PET-2-positive: eBEACOPP / PET-2-negative: standard eBEACOPP | Effect |
|---|---|---|---|---|
| PFSPET-2-negative cohort, per-protocol primary analysis | primaryBorchmann 2017 | 92.2% at 5 y (89.4–95.0%) | 90.8% at 5 y (87.9–93.7%) | Difference 1.4% (95% CI -2.7 to 5.4). Severe infections occurred in 40 (8%) of 498 patients with 4 cycles versus 75 (15%) of 502 with standard treatment; organ toxicities in 38 (8%) of 498 versus 91 (18%) of 502. Ten treatment-related deaths occurred in the trial: four in the PET-2-positive cohort and six in the PET-2-negative group. |
| PFSPET-2-positive cohort, randomised (434 patients, intention to treat as stated in the abstract for analyses other than the PET-2-negative primary analysis) | primaryBorchmann 2017 | 88.1% at 5 y (83.5–92.7%) | 89.7% at 5 y (85.4–94.0%) | P=0.46Log-rank P. The authors conclude that the outcome of patients treated with eBEACOPP could not be improved by adding rituximab after a positive PET-2. |
| Endpoint | Analysis | PET-2-positive: R-eBEACOPP / PET-2-negative: 4 cycles of eBEACOPP | PET-2-positive: eBEACOPP / PET-2-negative: standard eBEACOPP | Effect |
|---|---|---|---|---|
| PFSPET-2-negative cohort, per-protocol primary analysis | primaryBorchmann 2017 | 92.2% at 5 y (89.4–95.0%) | 90.8% at 5 y (87.9–93.7%) | Difference 1.4% (95% CI -2.7 to 5.4). Severe infections occurred in 40 (8%) of 498 patients with 4 cycles versus 75 (15%) of 502 with standard treatment; organ toxicities in 38 (8%) of 498 versus 91 (18%) of 502. Ten treatment-related deaths occurred in the trial: four in the PET-2-positive cohort and six in the PET-2-negative group. |
| PFSPET-2-positive cohort, randomised (434 patients, intention to treat as stated in the abstract for analyses other than the PET-2-negative primary analysis) | primaryBorchmann 2017 | 88.1% at 5 y (83.5–92.7%) | 89.7% at 5 y (85.4–94.0%) | P=0.46Log-rank P. The authors conclude that the outcome of patients treated with eBEACOPP could not be improved by adding rituximab after a positive PET-2. |
Appears in
Sources
Borchmann P, Goergen H, Kobe C, Lohri A, Greil R, Eichenauer DA, et al. PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group. Lancet. 2017;390(10114):2790-2802.