Overall Survival With Maintenance Olaparib at a 7-Year Follow-up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial

Resumen:
Because of nonspecific symptoms at disease presentation and inadequate screening methods, ovarian cancer is often advanced at the time of diagnosis results in a 10-year survival of 17% in patients with advanced epithelial ovarian cancer. The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib is the new standard of care in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 (BRCA) mutation. The SOLO1/GOG 3004 trial importantly found olaparib treatment resulted in a sustained progression-free survival (PFS) benefit in this patient population beyond the end of treatment and lasting up to 2 years, with a follow-up PFS analysis showing benefit up to 5 years. This analysis of the SOLO1/GOG 3004 cohort aimed to provide overall survival (OS) data up to 7 years following treatment of newly diagnosed advanced ovarian cancer with any PARP inhibitor. The SOLO1/GOG 3004 study included patients with newly diagnosed advanced high-grade serous or endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer with a germline or somatic BRCA1 and/or BRCA2 mutation. Patients were randomized (2:1) to receive olaparib tablets or placebo within 8 weeks of their last dose of chemotherapy surgery and received treatment for up to 2 years. This analysis of OS was conducted using a log-rank test stratified by response to first-line platinum-based chemotherapy with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated using a Cox proportional model. A total of 260 patients were randomly assigned to olaparib, and 130 of the 131 patients randomly assigned to placebo received study treatment. The median duration of follow-up for OS was 88.9 months (interquartile range, 85.7-93.6 months) in the olaparib group and 87.4 months (interquartile range, 84.3-91.7 months) in the placebo group. At the time of analysis, 149 of 391 patients had died. The median OS was not reached in the olaparib group compared with 75.2 months (95% CI, 65.4 months to not reached) in the placebo group, with an HR of 0.55 (95% CI, 0.40-0.76; P = 0.0004). This analysis was unadjusted for subsequent therapy, meaning the OS benefit was observed despite 44.3% of patients in the placebo group having received a PARP inhibitor in a subsequent line of therapy. On Kaplan-Meier estimate, 6.70% of olaparib patients versus 46.5% of placebo patients were alive 7 years after randomization. Of the patients randomized to olaparib, 45.3% of patients were alive and still yet to receive a first subsequent therapy after 7 years, compared with only 20.6% of patients randomized to placebo. Serious adverse events occurred in 21.2% of olaparib patients and 13.8% of placebo patients. The results of this follow-up survival analysis of the SOLO1/GOG 3004 study found that at a median follow-up time of 88 months, an HR for survival of 0.55 was observed with maintenance olaparib versus placebo. In addition, a considerable proportion of the olaparib patients were yet to receive a subsequent line of treatment compared with the placebo patients. De -spite these benefits, according to prespecified statistical criteria, improvement in OS with maintenance olaparib versus pla-cebo was not statistically significant.