Olaparib has solidified its place as a standard maintenance therapy for patients with platinum-sensitive relapsed ovarian cancer who have BRCA mutations. In the phase III SOLO 2 trial, the drug extended overall survival by more than a year in these patients compared with a placebo.
Olaparib (Lynparza; AstraZeneca) has solidified its place as a standard maintenance therapy for patients with platinum-sensitive relapsed ovarian cancer who have BRCA mutations. In the phase III SOLO 2 trial, the drug extended overall survival (OS) by more than a year compared with a placebo. Results were presented on May 29 at the 2020 American Society of Clinical Oncology Annual Meeting.
Around 50% of patients with ovarian cancer relapse after platinum-based chemotherapy, and those who relapse tend to have poor outcomes, living for a median of only 2 years. Thus, “the goals of treatment include delaying symptomatic disease progression and prolonging survival,” said Andrés Poveda, MD, of the Fundación Instituto Valenciano de Oncología in Valencia, Spain, who outlined the trial's results. About 5% to 15% of patients with ovarian cancer have BRCA1/2 mutations that make their cancer vulnerable to the PARP inhibitor olaparib.
Previously, the SOLO 2 trial showed that maintenance olaparib improved progression-free survival (PFS) by 13.6 months in patients with relapsed, platinum-sensitive, BRCA-mutant ovarian cancer compared with a placebo. These results, along with PFS findings from the earlier phase II Study 19 trial in patients with and without BRCA mutations, led to a 2017 FDA approval of the drug for these patients, regardless of BRCA status.
Yet, over the last two decades, “limited progress has been made in improving overall survival” in relapsed, platinum-sensitive ovarian cancer, Poveda said. This is due, in part, to the challenge of demonstrating an OS improvement in trials in which patients can cross over to the treatment arm. Further, patients have multiple treatment options following disease progression.
However, SOLO 2 demonstrated convincingly that olaparib can improve OS. Patients enrolled in the trial received at least two prior platinum-based chemotherapies and were responding to the one they received most recently. For 196 patients treated with olaparib, the median OS was 4.3 years, compared with 3.2 years in 99 patients who received a placebo. After 5 years, 42% of patients in the olaparib arm were still alive and 28.3% had not required subsequent treatment, compared with 33% and 12.8%, respectively, of patients in the placebo arm.
Overall, 22% of patients in the olaparib group continued taking the agent for at least 5 years, which Poveda considers “impressive in the setting of relapsed ovarian cancer.” Side effects, such as nausea, fatigue, vomiting, and anemia, caused a dose reduction in 28% of patients treated with olaparib and led 17% to stop treatment, compared with 3% for both dose reduction and treatment discontinuation in patients receiving a placebo.
“SOLO 2 is the first randomized phase III trial to provide overall survival data on a maintenance PARP inhibitor in this setting,” Poveda said. With the addition of long-term OS data, “this study helps usher in a new era of personalized medicine for women with this difficult-to-treat cancer,” he added.
Ursula Matulonis, MD, of Dana-Farber/Harvard Cancer Center in Boston, MA, who was not involved in the trial, was impressed by the results. “In SOLO 2, there was an OS benefit for the patients receiving olaparib versus placebo despite the fact that 39% of patients on the placebo arm eventually crossed over to a PARP inhibitor,” she said, noting that the trial was a follow-up to Study 19, which had suggested a more pronounced PFS benefit in patients with BRCA mutations.
However, olaparib has already been the standard of care in these patients for a few years based on its 2017 FDA approval, Matulonis said. Moreover, in late 2018 the FDA approved olaparib as a first-line maintenance therapy in patients with BRCA-mutant advanced ovarian cancer who are responding to platinum-based chemotherapy, “so olaparib and other PARP inhibitors are being increasingly used in newly diagnosed patients rather than waiting for recurrence.” –Catherine Caruso