Olaparib regimen extends survival for certain women with advanced ovarian cancer
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Maintenance therapy with olaparib and bevacizumab extended survival for women with newly diagnosed advanced ovarian cancer with homologous recombination deficiency, according to study results.
The findings — presented at European Society for Medical Oncology Congress — showed benefit with the combination despite the fact a high percentage of patients in the control arm received poly(ADP-ribose) polymerase (PARP) inhibitor therapy after progression.
The results confirm the regimen as the standard of care in this setting, Isabelle Ray-Coquard, MD, PhD, medical oncologist at Comprehensive Cancer Center Leon Bérard in France, and colleagues concluded.
Olaparib (Lynparza; AstraZeneca, Merck) is a PARP inhibitor approved in the United States for multiple cancer indications.
Ray-Coquard and colleagues conducted the PAOLA-1/ENGOT-ov25 trial to assess the addition of olaparib to maintenance bevacizumab (Avastin, Genentech) for women with advanced ovarian cancer with no evidence of disease after surgery or response to first-line platinum-based chemotherapy.
Researchers randomly assigned women 2:1 to 15 mg/kg bevacizumab every 3 weeks plus either 300 mg olaparib twice daily (n = 537) or placebo (n = 269) for up to 24 months.
PFS served as the primary endpoint. OS in the intention-to-treat population served as a key secondary endpoint.
As Healio previously reported, results presented at ESMO in 2019 showed the regimen significantly extended PFS (HR = 0.59; 95% CI, 0.49-0.72). Women with homologous recombination deficiency (HRD)-positive disease — defined as BRCA1/BRCA2 mutation and/or genomic instability — derived particular benefit.
At ESMO this year, Ray-Coquard presented results of the prespecified final OS analysis. Median follow-up was 61.7 months in the olaparib-bevacizumab group and 61.9 months in the placebo-bevacizumab group.
Results showed no significant OS benefit in the intention-to-treat population with the addition of olaparib to maintenance therapy (median, 56.5 months vs. 51.6 months; HR = 0.92; 95% CI, 0.76-1.12). Researchers reported comparable 5-year OS rates with and without olaparib (47.3% vs. 41.5%).
However, results of an exploratory subgroup analysis showed the addition of olaparib to bevacizumab conferred a significant OS benefit among women with HRD-positive disease (HR = 0.62; 95% Ci, 0.45-0.85; 5-year OS rates, 65.5% vs. 48.4%). In this subgroup, the OS benefit with olaparib reached statistical significance among women with BRCA mutations (HR = 0.6; 95% CI, 0.39-0.93; 5-year OS rates, 73.2% vs. 53.8%) but not among those with no BRCA mutations (HR = 0.71; 95% CI, 0.45-1.13; 5-year OS rates, 54.7% vs. 44.2%.
Researchers observed no OS benefit with olaparib among women with HRD-negative disease (HR = 1.19; 95% CI, 0.88-1.63).
“For women facing an advanced ovarian cancer diagnosis who are HRD-positive, a targeted treatment in the first-line maintenance setting is critical to helping them live longer. These latest results at the 5-year landmark demonstrate that olaparib with bevacizumab reduces the risk of death by 38% in HRD-positive patients compared to bevacizumab alone, further reinforcing the clinically meaningful long-term survival benefit of this combination,” Ray-Coquard said in a press release issued by Merck and AstraZeneca. “This should be promising news for both clinicians and patients, as we see these additional data show that this combination may allow patients more time with family and loved ones. These results also highlight the importance of biomarker testing as part of a precision medicine approach to guide treatment decisions in ovarian cancer.”
A higher percentage of women in the control group than experimental group received subsequent PARP inhibitor therapy (45.7% vs. 19.6%).
Olaparib exhibited a safety profile consistent with that observed in prior trials. Researchers observed no new safety signals.
Nine women (1.6%) in the olaparib group and six (2.2%) in the control group developed myelodysplastic syndrome, acute myeloid leukemia or aplastic anemia. Twenty-two women (4.1%) in the olaparib group and eight (2.9%) in the control group developed any new primary malignancy.
Investigators reported rates of pneumonitis/interstitial lung disease/bronchiolitis of 1.3% in the olaparib group and 0.7% in the placebo group.
References:
- Lynparza (olaparib) in combination with bevacizumab, and as monotherapy, demonstrated clinically meaningful long-term survival in certain patients with first-line advanced ovarian cancer in exploratory analyses of two phase 3 trials. Available at: www.businesswire.com/news/home/20220909005050/en/LYNPARZA%C2%AE-olaparib-in-Combination-With-Bevacizumab-and-as-Monotherapy-Demonstrates-Clinically-Meaningful-Long-Term-Survival-in-Certain-Patients-With-First-Line-Advanced-Ovarian-Cancer-in-Exploratory-Analyses-of-Two-Phase-3-Trials. Published: Sept. 9, 2022. Accessed: Sept. 9, 2022.
- Ray-Coquard IL, et al. Abstract #LBA29. Presented at: European Society for Medical Oncology Congress; Sept. 9-13, 2022; Paris.
Perspective
Back to TopEva Chalas, MD
The OS advantage offered by the combination of olaparib and bevacizumab is sizable and warrants defining this combination as the new standard of care for patients with advanced-stage, high-grade ovarian carcinoma with platinum-sensitive disease. Analysis permits an individualized approach in demonstrating value only for HRD-positive tumors, with or without BRCA mutations. In addition, it quantifies risk of hematologic and new primary malignancy, which is valuable in obtaining informed consent.
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Ray-Coquard IL, et al. Abstract #LBA29. Presented at: European Society for Medical Oncology Congress; Sept. 9-13, 2022; Paris.
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