Phase III SOLO-2 Data Demonstrates High Survival Benefit of Olaparib

olaparib; ovarian cancer: olaparib; ovarian cancerMaintenance therapy with olaparib showed significant clinical benefit with a statistically significant improvement in progression-free survival (PFS) compared to placebo for patients with platinum-sensitive, relapsed, BRCA-mutant ovarian cancer, according to data presented by Eric Pujade-Lauraine, MD, PhD, of the University of Paris Descartes at the Society of Gynecologic Oncology's (SGO) 2017 Annual Meeting on Women's Cancer (Late Breaking Abstract 2). Trial Methodology The randomized, double-blind, phase III SOLO-2 study aimed to evaluate the efficacy and tolerability of olaparib tablets, an oral PARP inhibitor, as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer. The trial also sought to confirm findings from “a positive phase II trial in all-comer patients with platinum-sensitive relapsed ovarian cancer (Study 19; NCT00753545) that those having a BRCA1/2 mutation derived the greatest PFS benefit from olaparib,” according to investigators of the multicenter international trial. Eligible patients included those with platinum-sensitive relapsed ovarian cancer and a known BRCA mutation, as well as those who were in response to their most platinum-based chemotherapy after two or more lines of treatment. Researchers randomized patients 2:1 to maintenance olaparib 300 mg BID or placebo; treatment continued until the point of disease progression. Investigator-assessed PFS (RECIST 1.1) was the primary endpoint of the study. Trial methodology included a sensitivity of PFS, which was conducted by a blinded independent central review committee. Key secondary endpoints, included time to first subsequent therapy or death (TFST), time to second progression (PFS2), time to second subsequent therapy or death (TSST), overall survival, and safety and tolerability. Data analysis included 196 patients who received olaparib and 99 who received placebo. Researchers noted that baseline characteristics did not differ significantly between treatment groups. Fifty-four percent of patients receiving olaparib had attained partial response at time of enrollment compared to 53 percent of those in the placebo group. Forty percent of patients in each group had a platinum-free interval of 6-12 months. Forty-three percent of patients in the olaparib group had three more prior lines of therapy at enrollment compared to 37 percent in the placebo arm. SOLO-2 Results Late Breaking Abstract 2 Researchers found that olaparib achieved a statistically significant increase compared to placebo in PFS, by investigator assessment and BICR, and in PFS2. Data on overall survival is currently immature. Investigator-assessed median PFS in the olaparib arm was 19.1 months compared to 5.5 months in the placebo arm (HR, 0.30; 95% CI, 0.22-0.41; P <.0001). The pre-specified BICR analysis reported a median PFS of 30.2 months for patients treated with olaparib versus 5.5 months for placebo, which is a 75 percent reduction in the hazard for progression and death (HR, 0.25; 95% CI, 0.18-0.35; P <.0001). Median time to first subsequent therapy or death was significantly longer for the olaparib group compared to placebo (27.9 months vs. 7.1 months, respectively), according to researchers. Median PFS2 has not yet been reached in the olaparib arm, while the placebo cohort had a median PFS2 of 18.4 months. This represents a 50 percent reduction in the hazard ratio in favor of the PARP inhibitor, authors noted. Additionally, TSST was 18.2 months among patients in the placebo group; this endpoint has not yet been reached in the olaparib group. Adverse Events Researchers determined that the PARP inhibitor was generally well-tolerated with no new or unexpected treatment-associated adverse events among patients who received olaparib. Nausea was one of the most common adverse events in the olaparib and placebo groups (75.9% vs. 33.3%, respectively). Other common adverse events include fatigue/asthenia (65.6% vs. 39.4%), anemia (43.6% vs. 8.1%), vomiting (37.4% vs. 19.2%), and diarrhea (32.8% vs. 20.2%). Thrombocytopenia occurred in 13.8 percent of patients receiving olaparib compared to 3.0 percent in placebo. Additionally, researchers reported that neutropenia occurred in 19.5 percent of the olaparib group versus 6.1 percent of the placebo group. While toxicity was mostly low-grade, grade ≥3 adverse events included anemia (19.5% in olaparib vs. 2.0% in placebo), neutropenia (5.1% in olaparib vs. 4.0% in placebo), and thrombocytopenia (1.0% in both olaparib and placebo groups). Treatment discontinuation due to toxicity was 10.8 percent, according to investigators. “Patient-reported outcomes showed no detriment for olaparib in average change from baseline in the Trial Outcome Index score. “Olaparib tablet maintenance treatment in SOLO-2 led to a clinically meaningful, statistically significant PFS benefit in patients with platinum-sensitive relapsed ovarian cancer and a BRCA mutation,” researchers concluded. “Key endpoints of PFS by BICR and PFS2 substantiated the efficacy benefit. Maintenance treatment with the tablet formulation of olaparib was well-tolerated, with a low incidence of discontinuation due to toxicity.” Implications for Practice SOLO-2 is the first phase III trial of olaparib tablets as maintenance treatment and showed a significant benefit in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation, according to researchers at SGO. “The results of SOLO-2 further demonstrate the efficacy and significant clinical value of olaparib for women faced with this devastating disease that strikes when women are in the prime of their lives,” Allan Covens, MD, Professor and Chair of the Division of Gynecologic Oncology at the University of Toronto and Sunnybrook Health Sciences Centre, commented in a statement. “This study shows that this treatment can make a meaningful difference for patients with BRCA-mutated ovarian cancer, potentially extending their cancer-free lives by over 2 years.” Richard Penson, MD, co-author and Associate Professor of Medicine at Harvard Medical School and Clinical Director of Medical Gynecologic Oncology at Massachusetts General Hospital, emphasized the value of the study in a statement, noting the “SOLO-2 clinical data were practice changing given the magnitude of benefit, with patients on placebo experiencing recurrence within 6 months and olaparib extending this to more than 2 years. “The SOLO-2 data demonstrated a statistically significant and clinically meaningful improvement in outcomes for those who took olaparib,” concluded Penson. “The results, which showed a delay in disease progression in the maintenance setting, highlight the impact of PARP inhibition at the forefront of the important advances we are making in targeting ovarian cancer.” Catlin Nalley is associate editor.

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