The risk for secondary hematologic malignancies is not increased significantly in women with advanced ovarian cancer who are treated with poly (ADP-ribose) polymerase (PARP) inhibitor maintenance or as first-line treatment.
In a combined meta-analysis of 7 phase 3 randomized controlled trials of women with advanced ovarian cancer, the overall incidence of secondary hematologic malignancies was 0.80% in the women randomized to PARP inhibitors as maintenance compared with 0.47% in controls (risk ratio [RR], 1.45; 95% confidence interval [CI], 0.68-3.07; P = .34).
The data were reported by Thura W. Htut, MBBS, MRCP, Haematology Fellow, Aberdeen Royal Infirmary, Scotland, UK, and colleagues in poster format at the 2020 virtual scientific program of the American Society of Clinical Oncology.
A total of 4445 patients were included from the ARIEL3, ENGOT-OV16/NOVA, and SOLO-2 clinical trials in which PARP inhibitors were studied in the treatment of recurrent ovarian cancer, and VELIA, PRIMA, SOLO-1, and PAOLA-1 clinical trials in which PARP inhibitors were studied as first-line treatment. Treatment regimens in the study arm were olaparib (Lynparza), niraparib (Zejula), rucaparib (Rubraca), veliparib, or olaparib plus bevacizumab (Avastin), while the control arm consisted of placebo or bevacizumab. Randomization was 2:1 in all studies.
In patients with newly diagnosed ovarian cancer (N = 3044), the incidence of a secondary hematologic malignancy was 0.59% in the group randomized to PARP inhibitors compared with 0.09% in the control group. Despite a numeric trend toward increased incidence in patients receiving PARP inhibitors, the difference was not statistically significant (RR, 2.7; 95% CI, 0.7-10.37; P = .15).
In women with recurrent ovarian cancer (N = 1401), secondary hematologic malignancy rates were identical, developing in 1.28% of the PARP inhibitor and control arms (RR, 0.96; 95% CI, 0.38-2.46; P = .94).
Estimates were derived for patients treated with olaparib or niraparib within the PARP inhibitor group. For those treated with olaparib, the rate of secondary hematologic malignancy was 1.3% compared with 1% in the controls (RR, 1.24; 95% CI, 0.46-3.31; P = .67). Among patients assigned to niraparib, the rates were identical, with 0.47% developing a secondary hematologic malignancy in both the niraparib and control groups (RR, 1.28; 95% CI, 0.30-5.45; P = .74).