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Poly (ADP-ribose) polymerase (PARP) inhibitor regimens for ovarian cancer in phase III randomized controlled trials:
Introduction:
We 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.
Methods:
A 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.
Results:
Network 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.
Conclusions:
The 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.
Insights
Poly (ADP-ribose) polymerase (PARP) inhibitor regimens show similar efficacy and toxicity in BRCA-mutated ovarian cancer. Cost-effectiveness analysis suggests upfront combination PARPi regimens are not ideal, with upfront treatments being less toxic.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Ovarian cancer with BRCA mutations presents challenges for treatment selection.
- Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a key therapeutic class.
- Evaluating different PARPi regimens in various treatment settings is crucial.
Purpose of the Study:
- To compare the efficacy and toxicity of PARPi regimens in BRCA-mutated ovarian cancer.
- To assess the cost-effectiveness of these regimens using the ASCO value framework.
- To guide treatment decisions for both front-line and relapsed settings.
Main Methods:
- A network meta-analysis synthesized data from phase III randomized controlled trials.
- Primary outcomes included progression-free survival (efficacy) and grade 3-4 adverse events (toxicity).
- Cost-effectiveness was evaluated using the American Society of Clinical Oncology (ASCO) value framework.
Main Results:
- No statistically significant differences in efficacy or toxicity were found among upfront or relapsed PARPi regimens.
- All assessed PARPi regimens demonstrated similar clinical benefits, toxicity profiles, and net health benefits.
- The addition of bevacizumab to olaparib increased cost per unit net health benefit; upfront regimens were less toxic than relapsed ones.
Conclusions:
- Treatment decisions for PARPi regimens in BRCA-mutated ovarian cancer must balance efficacy, toxicity, and cost.
- Current combination PARPi regimens are not recommended upfront due to cost-effectiveness considerations.
- Upfront PARPi regimens exhibit lower toxicity compared to those used in the relapsed setting.
