REG is an active drug in non-adipocytic soft tissue sarcoma previously treated with doxorubicin (Mir et al. Lancet Oncol 2016). Efficacy of REG in PAZ pretreated pts is unknown. REGOSARC is a multi-cohort double-blind placebo (PLAC)-controlled phase II trial assessing the activity of REG in soft-tissue sarcoma previously treated with doxorubicin. Cross-over after centrally confirmed disease progression was allowed.
In the present subgroup analyses of the pooled study (cohorts B,C,D and E), we analyzed the magnitude of REG activity in pts with prior exposure to PAZ.
The total study population consisted of 176 pts (101 women, 57%), with a median age of 59 (20-81). with the following histologies (n/%): leiomyosarcoma (80/45), synovial sarcoma (28/16) or other sarcoma (68/39). Most pts had PS = 0 (N = 83, 47%) or PS = 1 (N = 92, 52%). Median time from initial diagnosis to study enrollment was 30 months (range, 5.6-498). Median follow-up was 59.6 months. 88 pts each were allocated to the REG and placebo (PLAC) arms, including 21 (24%) and 22 (25%) pts with previous PAZ exposure. Overall, the significant benefit of REG compared to PLAC in terms of PFS with a median PFS of 3.8 (REG) vs 1.0 months (PLAC); HR(REG/PLAC)=0.43 [95%CI: 0.32-0.59], p<.00001, was confirmed. The magnitude of the benefit did not significantly differ when assessed by prior PAZ exposure: HR(REG/PLAC)=0.33 [0.18-0.61] for those previously exposed to PAZ and 0.45 [0.32-0.65] for those not exposed to PAZ; interaction test in Cox model, p = 0.35. In the total study population non significant numerically higher median OS was observed in the REG arm:13.4 (REG) vs 9.0 months (PLAC), HR = 0.76 [0.56-1.03], p = 0.08. The magnitude of this difference was larger in pts previously exposed to PAZ: HR(REG/PLAC)=0.43 [0.22-0.85] (p = 0.015), vs HR = 0.88 [0.62-1.25] (p = 0.49) for those not exposed to PAZ; interaction test, p = 0.065. Safety has been previously reported (Mir et al. Lancet Oncol 2016; Penel ASCO 2019).
We conclude that prior exposure to PAZ did not significantly modify PFS advantage of REG. Benefit of REG in terms of OS could be larger in patients previously exposed to PAZ.
Clinical trial identification
Legal entity responsible for the study
Centre Oscar Lambret, Lille, France.
All authors have declared no conflicts of interest.