Abstract
Simple SummaryOvarian cancer (OC) is a leading cause of cancer-related death and 85% of women with advanced OC relapse after chemotherapy. First-line (1L) maintenance therapy is given to prolong the benefit of chemotherapy. However, selection of a 1L maintenance therapy is challenging given the number of therapies available and the lack of clinical trials that directly compare these therapies. Indirect treatment comparisons (ITCs) allow the comparison of therapies across trials and may inform selection of the most appropriate treatment option. ITCs must follow statistical principles to ensure similarity among trials and allow for a fair comparison. This study assessed whether two types of ITC could be performed to compare the poly(ADP-ribose) polymerase inhibitor niraparib with other 1L maintenance therapies. The 12 clinical trials assessed differed too significantly to meet recommended criteria for comparison. This study highlights the need for caution when comparing trial data to inform treatment decisions.Selecting a first-line (1L) maintenance option for ovarian cancer is challenging given the variety of therapies, differing trials, and the lack of head-to-head data for angiogenesis and poly(ADP-ribose) polymerase (PARP) inhibitors. Thus, indirect treatment comparisons (ITCs) can aid treatment decision making. This study assessed the feasibility of two ITCs, a network meta-analysis (NMA) and a population-adjusted ITC (PAIC), comparing the efficacy of the PARP inhibitor niraparib in the PRIMA trial (NCT02655016) with other 1L maintenance treatments. A systematic literature review was conducted to identify trials using the Cochrane Handbook for Systematic Reviews of Interventions to assess differences in trial design, population characteristics, treatment arms, and outcome measures. All 12 trials identified were excluded from the NMA due to the absence of a common comparator and differences in survival measures and/or inclusion criteria. The PAIC comparing PRIMA and PAOLA-1 trials was also not feasible due to differences in inclusion criteria, survival measures, and the previous receipt of chemotherapy/bevacizumab. Neither ITC met recommended guidelines for analysis; the results of such comparisons would not be considered appropriate evidence when selecting 1L maintenance options in ovarian cancer. ITCs in this setting should be performed cautiously, as many factors can preclude objective trial comparisons.
Highlights
In the age of precision medicine, oncologists have a variety of therapeutic options, supported by a large amount of clinical data, and are challenged to select the optimal therapy based on the benefit:risk profile for each patient, while considering the uncertainty of their disease course [1]
These trials included eight monotherapy options comprised of Poly(ADP-ribose) polymerase (PARP) inhibitors, a peptide inhibitor, an anti-cancer antigen-125 (CA-125) monoclonal antibody, tyrosine kinase pathway inhibitors, an anti-vascular epithelial growth factor mAb, and one combination regimen
Only niraparib, olaCancers 2022, 14, x FOR PEER REVIEWparib, and bevacizumab plus olaparib have been approved for use as maintenance the6raopfie1s6 following 1L chemotherapy [37–39]
Summary
In the age of precision medicine, oncologists have a variety of therapeutic options, supported by a large amount of clinical data, and are challenged to select the optimal therapy based on the benefit:risk profile for each patient, while considering the uncertainty of their disease course [1]. For oncologists who treat women with ovarian cancer, this is a particular challenge when selecting a maintenance therapy following first-line (1L) chemotherapy [2]. Several randomized controlled trials (RCTs) have demonstrated the benefit of 1L maintenance therapy in delaying disease recurrence or progression and prolonging the time between chemotherapy regimens, which is an important predictor of response to subsequent treatments [3,7,9,10]. Poly(ADP-ribose) polymerase (PARP) inhibitors, including niraparib, rucaparib, and olaparib, have revolutionized the treatment of advanced ovarian cancer [3]. These agents provide maintenance therapy options that prolong progressionfree survival (PFS), have manageable toxicity profiles, and delay the subsequent use of chemotherapy and the impact of the associated toxicities on quality of life in women with advanced ovarian cancer [3,7,9,15]
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