SOLO1 and SOLO2: Randomized phase III trials of olaparib in patients (pts) with ovarian cancer and a BRCA1/2 mutation (BRCAm)

Background: In a pivotal Phase II trial (NCT00753545 ), maintenance treatment with the oral PARP inhibitor olaparib (400 mg bid; capsules) led to a significant PFS improvement vs placebo in pts with platinum-sensitive, relapsed serous ovarian cancer (Ledermann et al NEJM 2012), with the greatest PFS benefit seen in pts with a BRCAm (HR=0.18, 95% CI 0.10-0.31, P<0.00001; Ledermann et al ASCO 2013). Two AstraZeneca-sponsored Phase III trials of olaparib maintenance monotherapy have been initiated in ovarian cancer pts with a BRCAm: SOLO1 (NCT01844986 ); SOLO2 (NCT01874353 ). Methods: SOLO1 and SOLO2 are double-blind multicenter studies in which pts are being randomized (2:1) to receive olaparib (300 mg [2 x 150 mg tablets] bid) or placebo. Both trials are recruiting pts with high-grade serous or endometrioid ovarian cancer, including primary peritoneal and/or fallopian tube cancer, who have a known deleterious (or suspected deleterious) BRCAm and who are in complete or partial response following the completion of platinum-based chemotherapy. To be eligible for SOLO1, pts must have newly diagnosed, advanced (FIGO stage III-IV) disease and have responded to first-line platinum therapy, whereas pts in SOLO2 must have completed ≥2 lines of platinum therapy. All eligible pts will have a BRCAm and will undergo germline BRCA testing (Myriad Integrated BRACAnalysis) as part of the trials. For both trials, the primary objective is PFS by blinded independent central review using RECIST v1.1. Radiologic scans will be performed at baseline and every 12 weeks for 120 (SOLO1) or 72 (SOLO2) weeks, and every 24 weeks thereafter. Blinded treatment will continue until objective disease progression. Primary analyses will be performed at {approx}60% maturity using log-rank tests. Other objectives for both trials include: overall survival; time to earliest progression (RECIST or CA-125); time from randomization to second progression (PFS2); HRQoL; tolerability.