Olaparib prolongs PFS vs. chemotherapy in BRCA-mutated, platinum-sensitive ovarian cancer
CHICAGO — Olaparib monotherapy significantly improved overall response rates and PFS, with no new safety signals, compared with nonplatinum chemotherapy among women with germline BRCA-mutated, platinum-sensitive relapsed ovarian cancer, according to results of the randomized phase 3 SOLO3 study presented at ASCO Annual Meeting.
“SOLO3 is the first phase 3 randomized trial of a PARP [poly(ADP-ribose) polymerase] inhibitor vs. nonplatinum-based chemotherapy in women with [platinum-sensitive relapsed] germline BRCA-mutated ovarian cancer,” Richard T. Penson, MD, associate professor of medicine at Harvard Medical School and clinical director of medical gynecologic oncology at Massachusetts General Hospital, said during the presentation. “A statistically significant and clinically relevant improvement in [overall response rate] and PFS was observed with olaparib and chemotherapy vs. nonplatinum-based chemotherapy.”
Olaparib (Lynparza, AstraZeneca) demonstrated efficacy vs. pegylated liposomal doxorubicin in a randomized phase 2 trial that included women with BRCA-mutated ovarian cancer who experienced recurrence within 12 months of prior platinum therapy. The efficacy of pegylated liposomal doxorubicin, however, appeared higher than previously observed in this setting, according to study background.
In the confirmatory phase 3 study, Penson and colleagues randomly assigned 266 patients with BRCA-mutated, platinum-sensitive relapsed ovarian cancer in a 2:1 ratio to 300 mg twice-daily olaparib (n = 178) or physician’s choice of chemotherapy (n = 88) that included paclitaxel (n = 20), topotecan (n = 8), gemcitabine (n = 13) or pegylated liposomal doxorubicin (n = 47). Treatment continued until disease progression.
Researchers stratified women by chemotherapy treatment, prior lines of chemotherapy (2 to 3 vs. 4 or more) and platinum-free interval (6-12 months vs. more than 12 months).
ORR served as the trial’s primary endpoint. PFS and safety served as secondary endpoints.
Twelve patients in the chemotherapy group withdrew before receiving treatment, and 223 had baseline measurable disease (olaparib, n = 151; chemotherapy, n = 72).
Results showed an ORR of 72% in the olaparib group vs. 51% in the chemotherapy group (OR = 2.53; 95% CI, 1.4-4.58).
Patients in the olaparib group demonstrated significantly longer median PFS than the chemotherapy group as measured by blinded independent central review (13.4 months vs. 9.2 months; HR = 0.62; 95% CI, 0.43-0.91) and by investigator assessment (13.2 months vs. 8.5 months; HR = 0.49; 95% CI, 0.35-0.7).
The safety profiles of olaparib and chemotherapy were consistent with previous data, according to Penson. Common adverse events with olaparib vs. chemotherapy included nausea (65% vs. 34%) and anemia (50% vs. 25%). The most common adverse event with chemotherapy was palmar-plantar erythrodysesthesia (36% vs. 1%).
Serious adverse events occurred among 24% of patients in the olaparib group vs. 18% in the chemotherapy group. However, Penson noted that patients in the chemotherapy group appeared more than twice as likely (20% vs. 7%) to discontinue study treatment because of an adverse event.
“[Overall], SOLO3 provides important prospective data on the efficacy of these treatment options for women with heavily pretreated, PSR germline BRCA-mutated ovarian cancer,” Penson said. – by John DeRosier
Penson RT, et al. Abstract 5506. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: Penson reports consultant roles with and honoraria or travel expenses from AbbVie, Amgen, AstraZeneca, Baxalta, Clovis Oncology, Eisai, Genentech, Merck, Mersana, Sutter Medical Group, Tesaro and Vascular Biogenics; research funding from Array BioPharma, AstraZeneca, Cerulean Pharma, Eisai, Genentech, Regeneron, Sanofi, Tesaro and Vascular Biogenics; and patents with Blackwell Publishing. Please see the study for all other authors’ relevant financial disclosures.