SOLO2 Final Analysis Demonstrates ‘Unprecedented’ OS Boost

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The final results from the SOLO2/ENGOT-ov21 trial have been reported at the virtual 2020 ASCO Annual Meeting, confirming that maintenance olaparib significantly extends overall survival (OS) compared with placebo for women with BRCA mutation-positive, platinum-sensitive, relapsed ovarian cancer. 

The presenting author Andrés Poveda, from Hospital Quirónsalud in Valencia, Spain, reminded delegates that the trial’s primary analysis indicated that maintenance olaparib 300 mg twice daily had a “manageable tolerability profile” and achieved a median progression-free survival (PFS) gain of 13.6 months compared with placebo. 

The final analysis was planned for 60% data maturity for the 196 olaparib-treated patients and the 99 controls, all of whom had previously received at least two lines of platinum-based chemotherapy for relapsed high-grade serous or endometrioid ovarian cancer with a BRCA mutation, and had responded to their last platinum regimen. 

Median OS was 12.9 months longer with maintenance olaparib than placebo, at 51.7 versus 38.8 months and a significant hazard ratio (HR) for death of 0.74 in favour of the active agent. The 5-year OS rates were 42% and 33%, respectively. 

This outcome was achieved despite 38% of placebo-treated patients subsequently receiving PARP inhibitor therapy versus 10% of the olaparib arm, the presenter said. After adjusting for subsequent PARP inhibitor therapy in the placebo arm, median OS was 51.7 months with olaparib and 35.4 months with placebo, giving a significant HR of 0.56. 

After 5 years of follow-up, 28% of olaparib-treated patients and 13% of controls were alive and had not required further treatment. The median time to first subsequent therapy was 27.4 and 7.2 months, respectively, at a significant HR for treatment of 0.37. 

Median treatment duration in the final analysis was 29.1 months for the olaparib maintenance arm versus 13.1 months for controls, with 22% and 9% of the groups continuing treatment for at least 5 years, respectively, “reflecting the therapeutic benefit and manageable tolerability of olaparib”, said Andrés Poveda.  

He reported only a “small increase” in treatment-emergent adverse events (TEAEs) in the final versus primary analysis despite the longer follow-up. Grade 3 and more severe TEAEs occurred in 46% of the olaparib arm and 19% of those given placebo, with serious events occurring in 26% and 8%, respectively.  

TEAEs led to dose interruption in 50% and 19% of patients in the olaparib and placebo treatment arms, respectively, dose reduction in 28% and 3%, and discontinuation in 17% and 3%. 

During treatment, 8% of olaparib-treated patients developed myelodysplastic syndrome or acute myeloid leukaemia (MDS/AML) versus 4% of controls, the presenter noted, remarking that the “association with the number of prior platinum regimens, olaparib treatment and other potential risk factors is being explored.” 

“At 5 years, 42% of patients treated with olaparib were alive [and] 22% of patients remain on maintenance olaparib for more than 5 years, which is unprecedented in the setting of relapsed ovarian cancer”, Andrés Poveda concluded.  

He added that “MDS/AML incidences should be interpreted in the context of their late onset and the longer OS observed with olaparib versus placebo.” 

Reference 

Poveda A, Floquet A, Ledermann JA, et al. Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation. J Clin Oncol; 38: (suppl; abstr 6002). DOI: 10.1200/JCO.2020.38.15_suppl.6002.