The landscape of PARP inhibitor maintenance therapy in ovarian cancer continues to evolve as long-term survival data mature, with recent analyses reinforcing the critical importance of biomarker-driven patient selection while highlighting significant survival benefits in appropriately selected populations.
SOLO-1 Delivers Impressive Long-Term Survival Benefits
The phase 3 SOLO-1 trial has established olaparib as a cornerstone of maintenance therapy for newly diagnosed advanced ovarian cancer patients with BRCA mutations. At 7-year follow-up, the study demonstrated a remarkable 45% risk reduction in death for patients receiving olaparib compared to placebo, with a highly significant P value.
"The 7-year survival data showed 67% of patients were alive with olaparib versus 46.5% with placebo," noted Martin A. Martino, MD, medical director of gynecologic oncology at Ascension St. Vincent's, during a recent Case-Based Roundtable event in Jacksonville, Florida.
The trial enrolled patients with stage III high-grade or stage IV ovarian cancer harboring BRCA mutations who achieved complete or partial response following cytoreductive surgery and first-line chemotherapy. Patients were randomized 2:1 to receive olaparib or placebo for up to 2 years of treatment, with the majority (391 patients) having germline BRCA mutations.
Kevin Elias, MD, a gynecologic oncologist at the Cleveland Clinic, emphasized the magnitude of the initial progression-free survival benefit: "For women randomized to olaparib, the chances of progression or death were reduced by 70%."
Regulatory Changes Reflect Maturing Evidence Base
The FDA has recently updated its guidance on PARP inhibitor use based on long-term survival data. Following final analysis of the PRIMA trial, the agency restricted niraparib's indication to maintenance treatment for adult patients with advanced ovarian cancer with homologous recombination deficiency (HRD), including BRCA mutations.
"The FDA said that the benefit-risk profile for non-HRD positive patients is no longer favorable," Martino explained. "That used to be all comers. Now they limited it to HRD."
The PRIMA trial initially suggested potential benefit across broader patient populations, but as 3-year, 4-year, and 5-year overall survival data matured, the survival curves began crossing with no significant difference observed. In the HRD-proficient arm, 5-year overall survival was 29% versus 27%, while the HRD arm showed no difference at all.
PAOLA-1 Highlights Importance of Biomarker Selection
The PAOLA-1 trial evaluated olaparib plus bevacizumab in newly diagnosed ovarian cancer patients, revealing important insights about patient selection. The study enrolled patients with stage III or IV disease with no progressive disease following chemotherapy, using a 2:1 randomization to continue bevacizumab alone or add olaparib at 100 mg twice daily for 2 years.
Overall survival analysis showed median survival of 56.5 months for olaparib plus bevacizumab versus 51.6 months for bevacizumab alone (HR, 0.92; 95% CI, 0.76-1.12; P = 0.4118), with the confidence interval crossing 1.00. However, when stratified by biomarker status, significant benefit was observed only in the BRCA-mutated group.
"This is not what we're going to be doing for HRD-negative patients. That's a good takeaway," Martino noted.
Recurrent Disease Setting Shows Consistent Benefits
In the recurrent disease setting, SOLO-2 evaluated olaparib in patients with platinum-sensitive, relapsed ovarian cancer harboring germline BRCA mutations. All patients had received at least 2 prior lines of platinum-based chemotherapy and achieved response to their most recent regimen.
"In SOLO-2, PFS in the olaparib group was 19 months vs 5.5 months in the placebo group," Elias reported. At 5-year follow-up, 28.3% of patients in the olaparib arm versus 12.8% in the placebo arm remained alive and treatment-free, with overall survival rates of 42.1% versus 33.2%, respectively.
Clinical Practice Implications
The accumulating long-term data underscore the transformative impact of PARP inhibitors in ovarian cancer management while emphasizing the critical importance of appropriate patient selection. The consistent benefits observed across both newly diagnosed and recurrent settings in BRCA-mutated patients have established these agents as standard-of-care options.
"There was a significant benefit in the HRD population and the BRCA-mutated population in some of these studies; it really changed our management," Martino reflected. "We never used to do these. When I was a fellow, we didn't have them."
The evolving regulatory landscape reflects the maturation of clinical evidence, with biomarker-driven approaches becoming increasingly refined as long-term survival data provide clearer guidance on which patients derive meaningful benefit from PARP inhibitor maintenance therapy.
