Currently, there are limited therapies to prevent or delay recurrence in advanced ovarian cancer, with approximately 70% of patients having a recurrence within 3 years. The effectiveness of olaparib, an oral poly (ADP-ribose) polymerase inhibitor, in relapsed disease has been well-established; however, its benefit as a maintenance therapy in newly diagnosed advanced ovarian cancer is uncertain. In a recent study, researchers evaluated the efficacy of upfront maintenance therapy with olaparib in patients with newly diagnosed, advanced BRCA-positive ovarian cancer (Moore K, et al. N Engl J Med. 2018;379:2495-2505).
SOLO1 was a randomized, double-blind, placebo-controlled, phase 3 trial that enrolled 391 patients with newly diagnosed, histologically confirmed, advanced high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancers with germline or somatic BRCA mutations. All patients had cytoreductive surgery, received platinum-based chemotherapy, and had a complete or partial clinical response. The patients were randomized in a 2:1 ratio to olaparib 300 mg twice daily or to placebo for 2 years. The primary end point was progression-free survival (PFS), as assessed by the investigators.
After a median follow-up of 41 months, the risk for disease progression or death at 3 years was 70% lower with olaparib than with placebo (95% confidence interval, 0.20-0.41; P <.001). The placebo group had a median PFS of 13.8 months, whereas the median had yet to be reached in the olaparib arm. Furthermore, improvement in PFS was maintained after stopping treatment at 2 years.
Olaparib was well-tolerated and exhibited a safety profile that was consistent with what was observed in the relapsed setting. The most common grade ≥3 toxicities in patients who received olaparib were anemia (22%) and neutropenia (9%). The rates of adverse events that led to dose reduction or discontinuation were relatively low, with only 12% of patients discontinuing olaparib because of adverse events.
“In conclusion, the SOLO1 trial showed that the use of maintenance therapy with olaparib, as compared with placebo, after platinum-based chemotherapy provided a substantial benefit with regard to progression-free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation,” observed the researchers.