Summary
A meta-analysis demonstrated that the risk of secondary hematologic malignancies was not significantly increased among ovarian cancer patients who were treated with PARP inhibitors compared to a control arm, while still attaining survival benefits, according to findings presented at the ASCO 2020 Annual Meeting (Abstract 12076).
“Ovarian cancer is the leading cause of death from gynecologic cancers in women worldwide,” noted study author Thura Htut, MBBS, MRCP, Department of Hematology, Aberdeen Royal Infirmary. “PARP inhibitors prevent the repair of single-strand breaks and generate double-strand breaks in tumor cells and have recently shown survivor benefits in ovarian cancer. However, the impact on the risks of secondary hematologic malignancies remains uncertain.”
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Original Article
Secondary Hematologic Malignancies & Ovarian Cancer Patients Treated With PARP Inhibitors
Oncology Times
By Catlin Nalley
A meta-analysis demonstrated that the risk of secondary hematologic malignancies was not significantly increased among ovarian cancer patients who were treated with PARP inhibitors compared to a control arm, while still attaining survival benefits, according to findings presented at the ASCO 2020 Annual Meeting (Abstract 12076).
“Ovarian cancer is the leading cause of death from gynecologic cancers in women worldwide,” noted study author Thura Htut, MBBS, MRCP, Department of Hematology, Aberdeen Royal Infirmary. “PARP inhibitors prevent the repair of single-strand breaks and generate double-strand breaks in tumor cells and have recently shown survivor benefits in ovarian cancer. However, the impact on the risks of secondary hematologic malignancies remains uncertain.”
To fill this knowledge gap, the researchers performed a combined meta-analysis of randomized controlled trials (RCT) to determine the risks of secondary hematology malignancies in patients with advanced ovarian cancer treated with PARP inhibitors.
Research Specifics
A comprehensive literature search was conducted using MEDLINE, EMBASE databases, and meeting abstracts through January 2020. Researchers also reviewed the references of potential studies for any other relevant research.
Keywords searched included: olaparib, rucaparib, niraparib, veliparib, PARP inhibitors, and ovarian cancer. Searches were limited to humans and randomized controlled trials. Studies written in English and non-English languages were obtained.
Eligible studies were phase III RCTs utilizing PARP inhibitors among ovarian cancer patients that mention secondary hematologic malignancies in the side effects.
“We used Mantel-Haenszel (MH) to calculate estimated pooled risk ratio (RR) with 95% confidence interval (CI),” noted Htut. “Heterogeneity was assessed with I2 and Cochran's Q- statistic. A P value of less than 0.05 were consider significant. Fixed effects model was applied.”
A total of 4,445 patients with advanced ovarian from seven phase III RCTs were included. “The study arm used olaparib, niraparib, rucaparib, veliparib, or olaparib plus bevacizumab while the control arm utilized placebo or bevacizumab,” according to the study authors. “Randomization ratio was 2:1 in all studies. The I2 statistic for heterogeneity was 0, suggesting some heterogeneity among RCTs.”
The meta-analysis included the following studies: ARIEL3, VELIA, PRIMA, ENGOT-0V16/NOVA, SOLO-1, SOLO-2, and PAOLA-1.
“Overall, secondary hematologic malignancy incidence was 0.80 percent in the PARP inhibitor group versus 0.47 percent in the control group (RR 1.45; 95% CI: 0.68 – 3.07, P = 0.34),” reported Htut. “In patients with newly diagnosed cancer, the incidence was 0.59 percent in the PARP inhibitors group versus 0.09 percent in the control group (RR 2.7; 95% CI: 0.7—10.37, P = 0.15).
“Among the recurrent ovarian cancer subset (n = 1,401), 1.28 percent developed secondary hematologic malignancies in both the study and control arms (RR 0.96; 95% CI: 0.38-2.46, P = 0.94),” he continued.
The researchers reported secondary hematologic malignancy in 1.3 patient in the olaparib subgroup compared to 1 percent in the control group with a RR of 1.24 (95% CI: 0.46-3.31, P = 0.67). Additionally, secondary hematologic malignancy occurred in 0.7 percent in the niraparib subgroup compared to 0.47 percent in the control group with RR of 1.28 (95% CI: 0.30-5.45, P = 0.74).
“Our study demonstrated that the risk of secondary hematologic malignancies was not significantly increased in patients who received PARP inhibitors compared to the control arm, despite attaining survival benefits,” Htut concluded. “Further studies and long term follow up are necessary in the future to define the actual relation and definitive incidence.”
Catlin Nalley is a contributing writer.