Phase III Randomised, Double Blind, Placebo Controlled Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed BRCA Mutated Ovarian Cancer Patients With a Complete or Partial Response Following Platinum Based Chemotherapy (SOLO-2)

gBRCA MUT with Pt-sensitive recurrence and CR or PR in most recent Pt-based therapy, ≥ 2 Pt-based regimens

295; median 2 prior therapies

Maintenance

Double Blind, Randomized

PFS, OS, PFS2, TFST, TSST, TTSP, evaluated per RECIST

gBRCA1/2 MUT

Ola maint (n=196) vs Placebo (n=99):

PFS: 19.1 vs 5.5 months, HR: 0.30 (0.22-0.41, p<0.0001)
PFS (BICR): 30.2 vs 5.5 months, HR: 0.25 (0.18-0.35, p<0.0001)
OS: 51.1 vs 38.8 months, HR: 0.74 (0.54-1.00, p=0.054)
TFST: 27.9 vs 7.1 months, HR: 0.28 (0.21-0.38, p=0.0001)
TSST: NR vs 18.2 months, HR: 0.42 (0.26-0.53, p=0.0001)
PFS2: NR vs 18.4 months, HR: 0.50 (0.34-0.72, p=0002)

Ola maint (n=196) vs Placebo (n=99) (adjusted for subsequent PARP inhibitor therapy in Placebo group):
OS: 51.7 vs 35.4 months, HR: 0.56 (0.35-0.97)

Exploratory analysis: Response to platinum or non-platinum chemotherapy after RECIST progression
at time of analysis progression in 54% of patients on Ola maint vs 81% of patients on Placebo

Placebo (n=69) vs Ola maint (n=78)
TTSP after any chemotherapy: 12.1 vs 6.9 months, HR: 2.17 (1.47-3.19)
TTSP after platinum chemotherapy: 14.3 vs 7 months, HR: 2.89 (1.73-4.82) 
TTSP after non-platinum chemotherapy: 6.0 vs 8.3 months, HR: 1.59 (0.86-2.90)  

Ola vs Placebo:
Serious AE: any (26 vs 8%), MDS/AML (4 vs 0% - within study safety follow up time; 8 vs 4% - after 5.4 years follow up)
Grade 3-4 AE: overall (46 vs 19%), anemia (21 vs 2%)

Improved PFS and OS with olaparib maintenance treatment for gBRCA MUT patients

Pujade-Lauraine E et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol (2017) 18:1274-84
https://www.ncbi.nlm.nih.gov/pubmed/28754483

Poveda A et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol (2021) 22(5):620-631
https://pubmed.ncbi.nlm.nih.gov/33743851/

Frenel JS et al. Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial. Ann Oncol (2022) 33(10):1021-1028
https://pubmed.ncbi.nlm.nih.gov/35772665/