The 10-year follow-up of HD9r demonstrated significant improvement in long-term freedom from treatment failure (FFTF) and OS for BE in advanced-stage HL. OS was 86%, 80% and 75% for BE, SB and COPP-ABVD, respectively, with P=0.01 for BE versus COPP-ABVD. Complete remission (CR) was achieved in 96% of patients with BE, 88% SB, and 85% with COPP/ABVD, as noted in table 2.
Table 2: Outcome of Treatment and Survival Rates in HD9r
Image 1: Kaplan-Meier analysis of the probability of (A) freedom from treatment failure and (B) overall survival in each treatment arm.r
Image 2: Forest plot of comparison: Analysis of Overall Survivalr
Image 3: Forest plot of comparison: Analysis of Progression Free Survivalr
©Cochrane Library 2017
In the RATHL studyr, 1129 patients with stage IIB-IV or IIA with adverse features, underwent interim PET-CT after 2 cycles of ABVD chemotherapy. PET-negative patients were randomised to ABVD or AVD, (doxorubicin, vinblastine and dacarbazine), while PET-positive patients were treated with 4 cycles of BE (or 6 cycles of BEACOPP-14). This study demonstrated that in those who were PET-positive (n=172) and had their treatment intensified to BEACOPP, 5-year progression-free survival (PFS) was 65% which is superior compared with historical data of continuing with ABVD. Similar results were achieved with escalation to BE in the SWOG 0816 studyr for patients who were interim PET-positive after 2 cycles of ABVD.
In AHL2011r, a randomised, non-inferiority phase 3 multicentre study for newly diagnosed stage III, IV or IIB HL, patients received standard therapy (6 cycles of BE) or PET-driven therapy (2 cycles of BE, followed by PET-2). Patients who were PET-2-negative de-escalated to 4 cycles of ABVD, while PET-2 positive patients continued with initial therapy followed by PET-4 to assess response for consideration of salvage therapy. 5-year PFS was 86% in the standard treatment group versus 85·7% in the PET-driven treatment group.
The HD18 study investigated giving fewer chemotherapy cycles to patients with advanced HL who achieved a complete metabolic remission after 2 cycles of BE, while rituximab was added to treatment in patients with positive PET-2. Rituximab had no impact on survival in PET-2 positive patients: 5-year PFS 89.7% vs 88.1%. In the PET-2 negative patients, the study demonstrated non-inferiority of 4 vs 6 cycles of BE, with 5-year PFS at 92 and 91%, respectively.