RATHL
A Randomized Phase III Trial to Assess Response Adapted Therapy Using FDG-PET Imaging in Patients With Newly Diagnosed, Advanced Hodgkin Lymphoma
Phase 3N = 1,214NCT00678327
- Population
- Previously untreated adults (18 years or older) with advanced classic Hodgkin lymphoma, defined as Ann Arbor stage IIB to IV, or stage IIA with bulky disease or at least three involved sites (full text).
- Design
- International randomised trial. After a baseline PET-CT and two cycles of ABVD, an interim PET-CT was centrally reviewed on a 5-point scale. Patients with negative findings were randomised to continue ABVD or omit bleomycin (AVD) in cycles 3 through 6; patients with positive findings received BEACOPP (not randomised). Radiotherapy was not recommended after negative interim scans. Primary outcome: difference in 3-year progression-free survival between the randomised groups, a non-inferiority comparison to exclude a difference of 5 or more percentage points. 1214 patients were registered (1203 eligible, per the full text).
- Primary endpoint
- PFS
- Arms
- ABVD (PET-negative, randomised) (control, n = 470): Continued ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in cycles 3 through 6 after a negative interim PET-CT
- AVD (PET-negative, randomised) (experimental, n = 465): AVD (ABVD without bleomycin) in cycles 3 through 6 after a negative interim PET-CT
- BEACOPP (PET-positive, not randomised) (experimental, n = 172): BEACOPP-14 or escalated BEACOPP after a positive interim PET-CT, chosen in advance by each treatment centre
- People
- Johnson P, senior author Barrington S, Cancer Research UK and University College London Cancer Trials Centre
Δ 36-month PFS−1.3 pointsΔ 36-month OS+0.4 pointsPFSHR 1.13 (95% CI 0.81–1.57)
Show the numbers
| Endpoint | Analysis | AVD (PET-negative, randomised) / BEACOPP (PET-positive, not randomised) | ABVD (PET-negative, randomised) | Effect |
|---|---|---|---|---|
| PFSRandomised patients with a negative interim PET-CT scan (ABVD and AVD groups) | primarymedian follow-up 41 monthsJohnson 2016 | 84.4% at 3 y (80.7–87.5%) | 85.7% at 3 y (82.1–88.6%) | Absolute difference in 3-year progression-free survival (ABVD minus AVD) 1.6 percentage points (95% CI -3.2 to 5.3). The authors write that the results fall just short of the specified non-inferiority margin of 5 percentage points. Respiratory adverse events were more severe in the ABVD group than in the AVD group. |
| OSRandomised patients with a negative interim PET-CT scan (ABVD and AVD groups) | primarymedian follow-up 41 monthsJohnson 2016 | 97.6% at 3 y (95.6–98.7%) | 97.2% at 3 y (95.1–98.4%) | Three-year overall survival; overall survival was a secondary outcome. |
| PFSRandomised patients with a negative interim PET-CT scan, intention-to-treat analysis (as labelled in Table 2 footnote of the open author manuscript) | primarymedian follow-up 41.2 monthsJohnson 2016 | — | — | HR 1.13 (95% CI 0.81–1.57)P=0.48Hazard ratio for AVD versus ABVD, two-tailed P for the null hypothesis of a hazard ratio of 1.00; 142 events of progression, relapse or death had occurred. Read in the open-access author manuscript (PMC4961236), Results, section 'Outcomes in the Randomized Group with Negative PET Findings'. |
| PFSPatients with a positive interim PET-CT scan treated with BEACOPP (not randomised; 172 patients) | primarymedian follow-up 41 monthsJohnson 2016 | 67.5% at 3 y | — | Single-group result with no comparator arm. 74.4% of these patients had negative findings on a third PET-CT scan. Three-year overall survival in this group was 87.8%. |
| Endpoint | Analysis | AVD (PET-negative, randomised) / BEACOPP (PET-positive, not randomised) | ABVD (PET-negative, randomised) | Effect |
|---|---|---|---|---|
| PFSRandomised patients with a negative interim PET-CT scan (ABVD and AVD groups) | primarymedian follow-up 41 monthsJohnson 2016 | 84.4% at 3 y (80.7–87.5%) | 85.7% at 3 y (82.1–88.6%) | Absolute difference in 3-year progression-free survival (ABVD minus AVD) 1.6 percentage points (95% CI -3.2 to 5.3). The authors write that the results fall just short of the specified non-inferiority margin of 5 percentage points. Respiratory adverse events were more severe in the ABVD group than in the AVD group. |
| OSRandomised patients with a negative interim PET-CT scan (ABVD and AVD groups) | primarymedian follow-up 41 monthsJohnson 2016 | 97.6% at 3 y (95.6–98.7%) | 97.2% at 3 y (95.1–98.4%) | Three-year overall survival; overall survival was a secondary outcome. |
| PFSRandomised patients with a negative interim PET-CT scan, intention-to-treat analysis (as labelled in Table 2 footnote of the open author manuscript) | primarymedian follow-up 41.2 monthsJohnson 2016 | — | — | HR 1.13 (95% CI 0.81–1.57)P=0.48Hazard ratio for AVD versus ABVD, two-tailed P for the null hypothesis of a hazard ratio of 1.00; 142 events of progression, relapse or death had occurred. Read in the open-access author manuscript (PMC4961236), Results, section 'Outcomes in the Randomized Group with Negative PET Findings'. |
| PFSPatients with a positive interim PET-CT scan treated with BEACOPP (not randomised; 172 patients) | primarymedian follow-up 41 monthsJohnson 2016 | 67.5% at 3 y | — | Single-group result with no comparator arm. 74.4% of these patients had negative findings on a third PET-CT scan. Three-year overall survival in this group was 87.8%. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 1.13 | 0.81–1.57 |