Molecular and clinical predictors of improvement in progression-free survival with maintenance PARP inhibitor therapy in women with platinum-sensitive, recurrent ovarian cancer: A meta-analysis
- Author(s)
- Lee, CK; Friedlander, ML; Tjokrowidjaja, A; Ledermann, JA; Coleman, RL; Mirza, MR; Matulonis, UA; Pujade-Lauraine, E; Bloomfield, R; Goble, S; Wang, P; Glasspool, RM; Scott, CL;
- Journal Title
- Cancer
- Publication Type
- epub ahead of print
- Abstract
- BACKGROUND: The authors performed a meta-analysis to better quantify the benefit of maintenance poly(ADP-ribose) polymerase inhibitor (PARPi) therapy to inform practice in platinum-sensitive, recurrent, high-grade ovarian cancer for patient subsets with the following characteristics: germline BRCA mutation (gBRCAm), somatic BRCA mutation (sBRCAm), wild-type BRCA but homologous recombinant-deficient (HRD), homologous recombinant-proficient (HRP), and baseline clinical prognostic characteristics. METHODS: Randomized trials comparing a PARPi versus placebo as maintenance treatment were identified from electronic databases. Treatment estimates of progression-free survival were pooled across trials using the inverse variance weighted method. RESULTS: Four trials included 972 patients who received a PARPi (olaparib, 31%; niraparib, 35%; or rucaparib, 34%) and 530 patients who received placebo. For patients who had germline BRCA1 mutation (gBRCAm1) (N = 471), the hazard ratio (HR) was 0.29 (95% CI, 0.23-0.37); for those who had germline BRCA2 mutation (gBRCAm2) (N = 236), the HR was 0.26 (95% CI, 0.17-0.39); and, for those who had sBRCAm (N = 123), the HR was 0.22 (95% CI, 0.12-0.41). The treatment effect was similar between the gBRCAm and sBRCAm subsets (P = .48). In patients who had wild-type BRCA HRD tumors (excluding sBRCAm; N = 309), the HR was 0.41 (95% CI, 0.31-0.56); and, in those who had wild-type BRCA HRP tumors (N = 346), the HR was 0.64 (95% CI, 0.49-0.83). The relative treatment effect was greater for the BRCAm versus HRD (P = .03), BRCAm versus HRP (P < .00001), and HRD versus HRP (P < .00001) subsets. There was no difference in benefit based on age, response after recent chemotherapy, and prior bevacizumab. CONCLUSIONS: In platinum-sensitive, recurrent, high-grade ovarian cancer, maintenance PARPi improves progression-free survival for all patient subsets. PARPi therapy has a similar magnitude of benefit for sBRCAm and gBRCAm. Although patients with BRCAm derive the greatest benefit, the absence of a BRCAm or HRD could not be used to exclude patients from maintenance PARPi therapy.
- Publisher
- Wiley
- Keywords
- BRCA mutation; homologous recombination deficiency; meta-analysis; platinum-sensitive recurrent ovarian cancer; poly(ADP-ribose) polymerase inhibitors
- Research Division(s)
- Cancer Biology And Stem Cells
- PubMed ID
- 33740262
- Publisher's Version
- https://doi.org/10.1002/cncr.33517
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-03-26 10:28:30
Last Modified: 2021-03-26 11:07:24