Olaparib maintenance is licensed in various countries for the treatment of platinum-sensitive relapsed ovarian cancer. The final analysis of the phase III SOLO2 trial reveals that the previously reported benefit in progression-free survival (PFS) obtained from olaparib maintenance in patients with relapsed, platinum-sensitive ovarian cancer harbouring a BRCA1/2 mutations, translates into a clinically meaningful survival benefit.
Olaparib maintenance provided a median OS benefit of 12.9 months compared with placebo in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Dr. Lybaert comments: “Olaparib has significantly changed the treatment algorithm for patients with ovarian cancer and convincingly claimed its place in the maintenance setting in recent years. Olaparib maintenance significantly delays disease progression in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation and as such, significantly delays the time before a new line of chemotherapy needs to be initiated and the associated toxicity. In addition, olaparib is globally well-tolerated making it easy to use in clinical practice.“
Relapsing ovarian cancer is characterized by consecutive lines of therapy with the time to relapse shortening with each successive line of treatment. The pivotal phase III SOLO2 trial was the first trial to demonstrate the efficacy of the PARP inhibitor olaparib in a maintenance setting for relapsed ovarian cancer patients with BRCA1/2 mutations, although survival data was immature at the time of primary analysis. Now, mature survival data is reported in this trial’s final analysis. This randomised, double-blind, placebo-controlled trial enrolled 295 platinum-sensitive relapsed ovarian cancer patients with high-grade serous or high-grade endometrioid disease with BRCA1/2 mutations to receive either olaparib (150mg twice daily) (N= 196) or placebo (twice daily) (N= 99) until disease progression.
The median age of patients in both groups was 56 years. In the olaparib group, 83% had a primary ovary tumour, compared to 87% receiving placebo. Between the two groups, 16% and 13%, respectively, had a primary fallopian tube tumour, 93% and 87% of patients had a serous histology and respectively 15% and 18% of patients had a ≥ 2cm lesion at baseline. BRCA1 mutations featured in 67% and 62% of patients, whilst BRCA2 mutations were found in 30% and 35% of patients. At the time of final analysis, the mean treatment duration was 29.1 months with olaparib and 13.1 months with placebo. After a median follow-up for overall survival (OS) of approximately 65 months, the difference in median OS with both regimens did not meet the threshold for statistical significance. However, with a median OS of 51.7 months with olaparib maintenance as compared to 38.8 months with placebo, it is clear that olaparib does induce a clinically meaningful survival benefit (HR[95%CI]: 0.74[0.54-1.00], p= 0.054). Olaparib maintenance also resulted in a better median time to first subsequent therapy or death, at 27.4 months, compared to 7.2 months with placebo (HR[95%CI]: 0.37[0.28-0.48]). Similarly, the median time to second subsequent therapy or death was 35.8 vs. 18.9 months, respectively (HR[95%CI]: 0.51[0.39-0.68]). Following disease progression, 10% and 38% of patients in the olaparib and placebo group received a subsequent PARP inhibitor either as maintenance following platinum-based chemotherapy or as monotherapy.
Dose interruptions due to treatment-emergent adverse events (TRAEs) occurred in 50% and 19% in the olaparib and placebo arm, respectively, translating into dose reductions in 28% and 3% of patients. Treatment discontinuation due to TRAEs occurred in 13% and 1%, respectively. The most common grade ≥3 TRAEs were anaemia (20% olaparib, 2% placebo), neutropenia (6% vs. 3%), fatigue and asthenia (6% vs. 2%), vomiting (3% vs. 1%) and abdominal pain (3% vs. 3%). TRAEs resulting in fatality occurred in 3% of olaparib patients, due to myelodysplastic syndrome and acute myeloid leukaemia.
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. S1470-2045(21): 00073-5.