Poly (ADP-ribose) polymerase (PARP) inhibitor regimens for ovarian cancer in phase III randomized controlled trials: a network meta-analysis

Abstract

IntroductionWe aimed to evaluate poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) regimens in BRCA-mutated ovarian cancer for patients responsive to front-line platinum (bevacizumab and olaparib, veliparib and chemotherapy, olaparib) or platinum-sensitive relapsed (olaparib, rucaprib, niraparib) patients in phase III randomized controlled trials.MethodsA network meta-analysis was utilized to generate the direct and indirect comparisons. The primary outcomes for network meta-analysis were efficacy (hazard ratios for progression-free survival in BRCA mutation cohort) and toxicity (odds ratios for all grade 3–4 adverse events). The American Society of Clinical Oncology (ASCO) value framework was used to assess the cost-effectiveness of the PARPi regimens.ResultsNetwork meta-analysis indicated no statistically significant differences in efficacy and toxicity among the assessed upfront or relapsed PARPi regimens (95% CI included 1). The ASCO value framework indicated that current PARPi regimens were similar in clinical benefits, toxicity, and net health benefit in the upfront (bevacizumab and olaparib, veliparib and chemotherapy, olaparib) and relapsed setting (olaparib, rucaprib, niraparib). The addition of bevacizumab to olaparib ($353.72) increased the cost per unit net health benefit for patients compared with olaparib monotherapy ($260.57). The upfront PARPi regimens had lower toxic scores than the regimens used at relapse.ConclusionsThe choice of PARPi regimens both in the upfront and relapsed setting should consider not only efficacy and toxicity but also costs in BRCA mutation patients. Current combining PARPi regimens are not recommended for such patients in the upfront setting from the cost-effective perspective. Upfront PARPi regimens are less toxic than those used at relapse.

Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305

“…It is worth noting that the performance of PARPi declines due to increased risks of selected adverse events, moreover, side effects have limited the clinical applicability of PARPi, especially in combination with already poorly tolerated chemotherapeutic agents ( Dellavedova et al, 2021 ). Additionally, not only from the efficacy and toxicity aspects, combining PARPi in therapeutic is not currently recommended from the cost-effective perspective ( Gong et al, 2020b ). Notably, PARP2 is particularly linked with the hematological toxicities, which arouse the interest of developing next-generation PARPi with improved selectivity for PARP1.…”

Poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis

“…The comparison between PARP inhibitors and placebo was recently investigated in other reviews [ 41 , 42 ]. PAOLA-1 [ 24 ] was not included in the study by Wang 2020, and Gong 2020 mainly focused on different regimens in BRCA-mutated ovarian cancer (newly diagnosed or relapsed) in his study.…”

Maintenance Treatment of Newly Diagnosed Advanced Ovarian Cancer: Time for a Paradigm Shift?

“…However, treatment decisions also need to take into account contraindications and the differences in tolerability profiles between PARP inhibitors, especially hematological events and the low occurrence of MDS and AML [41]. Cost effectiveness and regulatory access will also be a key consideration [42][43][44].…”