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The PARP inhibitor olaparib significantly improved progression-free survival as frontline maintenance therapy for women with BRCA-positive advanced ovarian cancer, according to findings from the randomized phase III SOLO-1 trial.
Kathleen N. Moore, MD
The PARP inhibitor olaparib (Lynparza) significantly improved progression-free survival (PFS) as frontline maintenance therapy for women with BRCA-positive advanced ovarian cancer, according to findings from the randomized phase III SOLO-1 trial presented at the 2018 ESMO Congress.
With a median follow-up of 41 months, the median PFS by independent central review was not reached in the olaparib arm (n = 260), versus 14.1 months in the placebo arm (n = 131). The investigator-assessed PFS in the olaparib arm was not reached, compared to 13.8 months in the placebo arm (HR, 0.30; 95% CI, 0.23-0.41; P <.0001). Although the median PFS for olaparib has not yet been reached, Moore said that it looks to be an approximate 3-year advantage over placebo.
"We feel that the SOLO-1 trial has demonstrated an unprecedented improvement in the progression-free survival in patients with a BRCA mutation who have advanced ovarian cancer when olaparib is incorporated following platinum-based chemotherapy,” said Kathleen Moore, MD, associate professor, Stephenson Cancer Center, University of Oklahoma, and principal investigator of SOLO-1, during a press conference at the meeting.
The ongoing SOLO-1 trial (NCT01844986) is evaluating maintenance olaparib following platinum-based chemotherapy in newly-diagnosed patients with advanced ovarian cancer with a BRCA1/2 mutation. Patients with newly diagnosed, FIGO stage III-IV, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer with germline or somatic BRCA mutations were enrolled. These patients must have also received cytoreductive surgery, and be in clinical complete response or partial response after platinum-based chemotherapy.
The study treatment in SOLO-1 continued until disease progression, and treatment was ceased for patients with no evidence of disease at 2 years. Although, patients with a partial response at 2 years could continue treatment.
Secondary endpoints of the trial were PFS2, which is defined as time from randomization to second progression event, overall survival, and quality of life.
Patients who received olaparib maintenance showed a statically significant improvement in PFS2, with a median PFS2 not reached, compared with 41.9 months in the placebo group (HR, 0.50; 95% CI, 0.35-0.72; P =.0002). Overall survival data are not yet mature, noted Moore. Regarding quality of life, there were no clinically relevant changes. The discontinuation rate in the olaparib arm was 12%.
“It is estimated that over 50% of women on the olaparib arm were still progression free at 4 years as compared to only 11% for placebo,” said Moore. “A key point here is that there was no change in the Kaplan-Meier curve at the 2-year mark when we stopped the olaparib or placebo therapy. So, it appears that the benefit of olaparib maintenance is extended beyond even the 2-year timepoint in which patients were receiving treatment.”
Adverse events (AEs) observed were low-grade, with the most common grade ≥3 AEs in the olaparib arm being anemia (22%) and neutropenia (8%). Baseline characteristics, including health-related quality-of-life scores, were balanced between the 2 arms.
“While ovarian cancer is a highly treatable disease due in large part to its exquisite chemosensitivity, the percentage of patients who survive disease-free for long periods of time is dismally low, and hovers in the 10% to 15% range,” Moore noted. “If we are going to make meaningful improvements on that rate, it has to be with improvements in frontline treatment.”
The majority of patients with ovarian cancer recur within 3 years of diagnosis, Moore said. Although their disease has the potential to be treated, those patients are no longer considered treatable. Moore emphasized the importance of SOLO-1, as it is the first phase III large prospective data set for this population of women.
“Maintenance olaparib should be considered standard treatment following platinum-based chemotherapy for women with newly diagnosed advanced ovarian cancer and a BRCA mutation,” concluded Moore.
Additionally, panelists at the press conference suggested that the field should be looking to the possibility of extrapolating this data to other high-grade serous carcinomas.
Olaparib is not currently approved by the FDA as a first-line maintenance treatment for newly diagnosed patients with BRCA-positive ovarian cancer. The PARP inhibitor is FDA approved for the maintenance treatment of recurrent ovarian cancer in response to platinum-based chemotherapy regardless of BRCA mutation status, and for the treatment of advanced ovarian cancer patients with a germline BRCA mutation previously treated with 3 or more lines of chemotherapy.
Moore K, Colombo N, Scambia G, et al. Olaparib maintenance therapy following first-line platinum-based chemotherapy in patients with FIGO stage III—IV ovarian cancer (OC) with a BRCA1/2 mutation (BRCAm): Phase III SOLO1 trial. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA7_PR.