Adverse Event Profile Following Maintenance Olaparib in Patients with BRCA-mutated Platinum-Sensitive Relapsed Serous Ovarian Cancer in the Phase III SOLO2 Trial

OBJECTIVE:To characterize the occurrence, duration, and outcomes of the most common non-hematological (nausea, vomiting, fatigue/asthenia) and hematological (anemia, neutropenia) adverse events experienced by patients receiving olaparib in the phase III SOLO2 trial. METHODS:SOLO2 (NCT01874353) is a randomized, double-blind, placebo-controlled trial. Eligible patients had histologically confirmed relapsed high-grade serous ovarian cancer or high-grade endometrioid cancer with a BRCA mutation and were in response after platinum-based chemotherapy. Patients were randomized 2:1 to olaparib tablets 300 mg twice daily (N = 196) or placebo (N = 99). Safety outcomes were analyzed in all randomized patients who received ≥1 dose of study drug (olaparib, n = 195; placebo, n = 99). RESULTS:The most common adverse events of interest (nausea, vomiting, fatigue/asthenia, anemia, and neutropenia) were generally reported early, within the first 1 to 3 months of olaparib treatment, and were mostly grade 1/2. For all adverse events of interest, the risk of experiencing an event was statistically significantly higher with olaparib than with placebo (nausea hazard ratio [HR] 3.38, p <.001; vomiting HR 1.86, p =.016; fatigue/asthenia HR 2.11, p <.001; anemia HR 5.80, p <.001; and neutropenia HR 2.66, p =.027). Of these adverse events, only nausea had a statistically significantly higher risk of experiencing a second event with olaparib than with placebo (HR 3.62, p <.001). The prevalence of nausea, fatigue/asthenia, and anemia was higher with olaparib than with placebo across all time points. The median time to resolution of the first adverse event for olaparib versus placebo was 1.7 versus 0.4 months (nausea), 2 versus 2 days (vomiting), 6.4 versus 2.3 months (fatigue/asthenia), 3.2 versus 2.9 months (anemia), and 29 versus 14 days (neutropenia). Fatigue/asthenia was the slowest adverse event to resolve. CONCLUSION:These data confirm that the use of olaparib as long-term maintenance therapy for patients with platinum-sensitive relapsed ovarian cancer is tolerable. Adverse events occurred early, were manageable, and few occurred with late onset.