Olaparib monotherapy superior to non-platinum chemotherapy in treatment of platinum-sensitive relapsed ovarian cancer
Penson presented interim results from the phase III SOLO3 trial, which tested the efficacy and safety of olaparib monotherapy in relapsed ovarian cancer patients with at least two prior platinum-based chemotherapy treatments. The results with the PARP inhibitor demonstrated significant and clinically relevant improvements in response rate and progression-free survival compared with chemotherapy in this group of patients.
In Europe, olaparib has been approved for the treatment of high-grade cancers of the ovaries, fallopian tubes and the peritoneum in patients whose cancer has been reduced or cleared by a platinum-based chemotherapy and who need continuing treatment. In the phase II trial of olaparib versus pegylated liposomal doxorubicin (PLD), olaparib showed efficacy in ovarian cancer patients with recurrence ≤12 months after prior platinum-based therapy. SOLO3 was set up to assess the efficacy and safety of olaparib monotherapy versus standard-of-care, based on physician's choice of single agent chemotherapy (i.e paclitaxel, topotecan, PLD, or gemcitabine) in platinum-sensitive or partially platinum-sensitive relapsed ovarian cancer patients.
SOLO3 is an open label, phase III study in which olaparib (300 mg bid) was compared to non-platinum-based chemotherapy. Included were patients with relapsed, high-grade serous or endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer. Patients, who had to have a germline BRCA1 or -2 mutation and be platinum-sensitive with at least 2 prior platinum-based chemotherapy lines, were randomised (2:1) to olaparib or chemotherapy. Primary endpoint was objective response rate by blinded independent central review (BICR). Secondary endpoints included progression-free survival (PFS), time to first subsequent therapy (TFST) and safety.
A total of 266 patients were randomised to olaparib (n=178) or chemotherapy (n=88). Patient characteristics were well balanced between groups. In the olaparib-arm, 72% achieved an objective response, with a complete response for 9%. In the chemotherapy arm this was significantly lower with 51% and 3%, respectively (odds ratio 2.53; 95% CI 1.40-4.58; p=0.002). The effect was strongest for patients with 2 prior lines of chemotherapy. PFS by BICR was 13.4 months and 9.2 months for olaparib and chemotherapy, respectively (HR 0.62; 95% CI 0.43-0.91; p=0.013). Median TFST as well, was longer in the olaparib-arm than for chemotherapy (15.1 months vs 10.2 months; p<0.001). Overall survival data was not mature yet and no clinical meaningful difference was found in health-related quality of life.
With a median treatment duration of 11.3 months, olaparib had a comparable amount of grade ≥3 adverse events to chemotherapy, which was associated with shorter treatment durations (PLD 6.0 months, paclitaxel 5.1 months, gemcitabine 3.3 months, topotecan 6.2 months). Patients in the chemotherapy arm were more than twice as likely to discontinue study treatment due to adverse events (20% vs 7%). The most common adverse events for olaparib (all grades) were nausea (64.6%), fatigue/asthenia (52.2%), and anemia (51.1%).
SOLO3 is the first randomised phase III trial of a PARP inhibitor versus non-platinum-based chemotherapy in women with platinum-sensitive relapsed ovarian cancer. Olaparib treatment was associated with improved ORR and PFS in comparison with non-platinum-based chemotherapy. The tolerability profiles of olaparib and chemotherapy were consistent with previously reported data. Taken together, these results provide important prospective data on treatment options for heavily pre-treated women with platinum-sensitive BRCA-mutated ovarian cancer.
Penson RT, Villalobos Valencia R, Cibula D, et al. Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial. Presented at ASCO 2019; abstract 5506.