An analysis of the phase III SOLO1 trial examined safety signals with olaparib maintenance therapy for women with newly diagnosed advanced ovarian cancer and a BRCA mutation.
An analysis of the phase III SOLO1 trial found no new safety signals when the PARP inhibitor olaparib was given as maintenance therapy for women with newly diagnosed advanced ovarian cancer and a BRCA mutation. Nausea, fatigue, and several other toxicities, including anemia, usually occur early in the course of treatment, suggesting better monitoring is needed in that early period.
“The tolerability profile of maintenance therapy with the PARP inhibitor olaparib in platinum-sensitive relapsed ovarian cancer is well characterized,” wrote study authors led by Nicoletta Colombo, MD, of the University of Milan-Bicocca in Italy, in a poster presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract 5539).
SOLO1 was the first trial evaluating the agent’s use in women with newly diagnosed advanced ovarian cancer. Previously, it showed that maintenance olaparib provides a substantial progression-free survival benefit compared with placebo, and the new analysis examined the safety profile in this new setting.
The analysis included a total of 260 patients treated with olaparib and 130 treated with placebo, with a median follow-up duration of approximately 41 months. The median duration of treatment was 25 months with olaparib and 14 months with placebo.
The most common adverse events of any grade included nausea (77% of olaparib patients vs 38% of placebo patients), fatigue/asthenia (63% vs 42%), vomiting (40% vs 15%), anemia (39% vs 10%), and others. Most adverse events were grade 1/2, though grade 3 anemia occurred in 22% of patients receiving olaparib and only 2% of those receiving placebo.
The median time to first onset of those most commonly reported adverse events was under 3 months for all. The median duration of the first adverse event was also under 3 months for all; it was 1.87 months in the olaparib group for anemia, compared with 1.64 months with placebo.
Nausea, fatigue/asthenia, anemia, thrombocytopenia, and several other common adverse events were generally managed with supportive therapy, dose interruption, and/or dose reduction. Twenty-three percent of olaparib patients required at least one blood transfusion, compared with 2% of placebo patients.
Three patients developed acute myeloid leukemia (AML) during the trial in the olaparib group (1.2%). There were no cases of AML or myelodysplastic syndrome in the placebo group. The time to onset of AML in those 3 patients was 173 days, 49 days, and 52 days after stopping olaparib; AML was fatal in all 3 cases.
“The tolerability profile of olaparib in patients with newly diagnosed ovarian cancer was consistent with that reported in the relapsed-disease setting, with no new safety signals identified,” the authors concluded. “Given that anemia predominantly occurred early, stricter monitoring is required at the beginning of treatment.”