Tolerability of olaparib tablets as maintenance therapy in patients with BRCA-mutated (BRCAm) platinum-sensitive relapsed serous ovarian cancer (PSR SOC): Phase III SOLO2/AGO-OVAR2.23 trial

Background:

In the SOLO2 trial (AGO OVAR 2.23), maintenance therapy with the PARP inhibitor olaparib significantly improved PFS vs. placebo (PBO) in BRCAm PSR SOC pts (HR 0.30, 95% CI 0.22 – 0.41, P < 0.0001; median 19.1 vs. 5.5 months) and was well tolerated (Pujade-Lauraine et al, SGO 2017). We analyzed AEs in SOLO2, the first study in PSR SOC to use the olaparib tablet formulation.

Methods:

Pts with BRCAm PSR SOC, who were in response to platinum chemotherapy, were treated with olaparib (300 mg bid; tablets; n = 195) or PBO (n = 99) until progression. AEs were graded by CTCAE v4.0.

Results:

The most common AEs with olaparib – nausea, fatigue/asthenia, anemia, and vomiting – were largely grade 1 – 2, though anemia was the most common grade ≥3 AE. AEs of fatigue/asthenia, vomiting and nausea generally improved as treatment continued, though fatigue/asthenia and anemia could last for several months (table). Most AEs were manageable by supportive treatment, dose interruptions (olaparib, 45%; PBO, 18%) and dose reductions (olaparib, 25%; PBO, 3%). Discontinuation of olaparib due to AEs was minimal (11%); anemia and neutropenia were the only AEs leading to discontinuation of olaparib in >one pt.

Conclusions:

Most AEs experienced by pts receiving olaparib tablets in SOLO2 were low grade and manageable. Initial nausea, vomiting and fatigue generally improved with ongoing treatment. The majority of AEs first occurred within the first three months of treatment. AEs causing treatment discontinuation were rare and mainly hematological.