Introduction: The weekly alternating SV regimen was compared to standard ABVD. An initial randomised phase II pilot study was carried out to determine tolerability and response rate, following which the study was expanded into a phase III trial.
Methods: Consenting patients (pts) with advanced HL (bulk disease, B symptoms and/or stage III/IV) were randomised between 6–8 cycles of ABVD or 12 weeks SV, to be followed in both arms by involved field irradiation (34–36Gy) to sites of initial bulk disease (>5cm) or splenic deposits, and to residual masses. In the phase III study radiotherapy was not required for ABVD pts who achieved complete remission. Drugs given were: ABVD (days 1 & 15): doxorubicin 25mg/m2, bleomycin 10000iu/m2, vinblastine 6mg/m2, dacarbazine 375mg/m2), q28. SV (mustine 6mg/m2, wks 1,5,9, doxorubicin 25mg/m2, wks 1,3,5,7,9,11, vinblastine 6mg/m2 wks 1,3,5,7,9,11, prednisone 40mg/m2 alternate days, vincristine 1.4mg/m2 wks 2,4,6,8,10,12, bleomycin 5000iu/m2 wks 2,4,6,8,10, 12, etoposide 60 mg/m2, 2 consecutive days wks 3,7,11). The primary outcome measure was progression-free survival (PFS). A total of 97 events were required to detect an improvement in 5-year PFS from 75% in ABVD to 85% in SV with a 5% significance level and 80% power.
Results: 520 pts were randomized (261 ABVD, 259 SV) between 3/98 and 10/06. Median age was 35. 49% had stage I/II disease with bulk and/or B symptoms, 29% stage III, 22% stage IV. 74% of pts overall had B symptoms and 52% bulk disease. International Prognostic Score (IPS) showed 37% 0–1, 54% 2–3 and 9% 4–7. The treatment groups were well matched for baseline prognostic factors. 95% SV pts completed 12 weeks, and 94% ABVD had 6 (71%) or 7/8 (23%) cycles. Pulmonary toxicity grade III/IV was reported in 37 pts (27 ABVD, 10 SV). More non-pulmonary grade III/IV toxicities were reported in SV(19%) than in ABVD (8%). Radiotherapy was given in 62% overall: 72% SV and 53% ABVD. The overall response rate (CR, CRu, PR) at completion of all treatment was 90% for SV and 89% for ABVD. There was one death due to toxicity on the ABVD arm, and none in SV. With a median 4 years follow up, 113 pts (55 ABVD, 58 SV) had recurrent disease or died with a hazard ratio of 1.10 (95% CI =0.76, 1.59; p=0.61) and 5-year PFS of 76% in ABVD and 74% in SV, absolute difference 2% (95% CI= −5%, 11%). 40 pts died (22 ABVD, 18 SV) with a hazard ratio of 0.81 (95% CI=0.44, 1,52; p=0.51) and 5-year overall survival (OS) of 90% in ABVD and 92% in SV, absolute difference 2% (95% CI -5%, 5%). Pre-planned analysis of sub-groups did not show significant variation in these results according to stage or IPS.
Conclusion: There is no evidence of a difference in PFS and OS between SV and ABVD in this trial, which made extensive use of consolidation radiotherapy and included a relatively favourable cohort. More pulmonary toxicity was reported for ABVD, while other toxicities were slightly higher with S V.
Disclosures: No relevant conflicts of interest to declare.