TOPLINE:

In patients with advanced epithelial ovarian cancer, first-line maintenance therapy with PARP inhibitors was associated with a progression-free survival benefit compared with standard chemotherapy alone, particularly for BRCA-variant and homologous recombination-deficient tumors, but did not demonstrate an overall survival benefit in any molecular subgroup. High-grade adverse events were also significantly more common with PARP inhibitors.

METHODOLOGY:

• Patients with advanced-stage epithelial ovarian, tubal, or peritoneal cancer have poor long-term survival outcomes. Standard options, which include primary cytoreductive surgery and platinum-based chemotherapy as well as neoadjuvant chemotherapy plus interval cytoreductive surgery and adjuvant chemotherapy, fail to prevent recurrence in most patients. The use of PARP inhibitors, particularly for BRCA-mutant and homologous recombination-deficient tumors, is a standard maintenance approach, but long-term benefits and associated risks remain uncertain.
• Researchers conducted a systematic review and meta-analysis of randomized clinical trials and prospective two-arm studies to evaluate the safety and efficacy of maintenance therapy with PARP inhibitors in patients with advanced-stage epithelial ovarian cancer who responded to first-line platinum-based chemotherapy.
• Overall, the analysis included seven randomized clinical trials involving 4013 patients, of whom 2619 received PARP inhibitor maintenance, and 1394 received standard chemotherapy alone.
• Primary outcomes were progression-free survival and overall survival; the secondary outcome was the incidence of severe adverse events. Researchers analyzed outcomes for patients with homologous recombination-deficient, BRCA-variant, BRCA wild-type, or homologous recombination-proficient tumors.

TAKEAWAY:

• Compared with standard chemotherapy alone, PARP inhibitor maintenance with standard chemotherapy was associated with improved progression-free survival in the overall population (hazard ratio [HR], 0.57) and in all molecular subgroups except homologous recombination-proficient tumors — BRCA-variant (HR, 0.40), homologous recombination-deficient (HR, 0.44), and BRCA wild-type (HR, 0.62).
• In the overall population, PARP inhibitor maintenance was associated with a 24% lower risk for recurrence or death than the control arm (relative risk [RR], 0.76), with the greatest effect observed in patients with homologous recombination-deficient or BRCA-variant tumors (RRs, 0.68 and 0.64, respectively).
• However, overall survival did not differ significantly in the overall population (HR, 0.94; 95% CI, 0.66-1.34) and was not significantly improved in any molecular subgroup. High-grade adverse events were also significantly more common in the PARP inhibitor group (HR, 2.40).
• In the overall population, the risk ratio for any recurrence or death varied across PARP inhibitor regimens, ranging from 0.53 for senaparib to 0.83 for olaparib. Similarly, for high-grade adverse events, the risk ratio ranged by treatment from 1.15 for veliparib to 4.73 for niraparib.

IN PRACTICE:

The variability in “efficacy, toxic effects, and long-term outcomes across subgroups and PARP inhibitor regimens suggests that treatment decisions should be individualized,” the authors of the study concluded, adding that “identification of predictive biomarkers and inclusion of patient-centered outcomes, such as quality-adjusted survival, should be prioritized to guide optimal maintenance strategies.”

SOURCE:

The study, led by Stamatios Petousis, PhD, Aristotle University of Thessaloniki, Thessaloniki, Greece, was published online in JAMA Network Open.

LIMITATIONS:

No direct head-to-head randomized comparisons between different PARP agents were available, limiting comparative conclusions. Overall survival data were mature for only some trials, which limited long-term survival inference. Additionally, adverse event and quality-of-life reporting were inconsistent across trials, reducing certainty about tolerability and patient-centered outcomes.

DISCLOSURES:

The study was supported by grants from the Swiss National Science Foundation, Gottfried and Julia Bangerter-Rhyner-Stiftung, Margarete and Walter Lichtenstein-Stiftung, and Freie Gesellschaft Basel. Some authors reported receiving grants or personal fees from various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.