Systematic literature review of efficacy and safety of first-line maintenance therapy trials in advanced ovarian cancer.

Aim: To review safety and efficacy outcomes in studies of first-line maintenance therapies for advanced ovarian cancer. Methods: A systematic literature review was performed (27 February 2020) to identify clinical outcomes including progression-free survival (PFS), overall survival (OS) and Grade ≥3 adverse events. Results: Overall 50 references met prespecified criteria; 18 studies evaluated 10 different agents, including PARP inhibitors. PFS was an end point in 16 trials and OS in 12 trials. PARP inhibitors reported better PFS hazard ratios (HRs: 0.59-0.68) compared with other classes; no mature OS data were identified. Safety reporting was inconsistent. Conclusion: Reported PFS HRs were better for PARP inhibitors than for other ovarian cancer maintenance therapies; overall survival data remain immature.

This article reports the results from a systematic literature review (SLR), enabling a critical and unbiased comparison of clinical studies, of responses and side effects of first-line maintenance therapies used for advanced ovarian cancer. Overall, this SLR supports the use of PARP inhibitors as maintenance therapy for patients with advanced ovarian cancer as they demonstrated a greater effect on delaying further disease progression than other drug types assessed. However, due to large differences between the clinical studies included (e.g. design of the trial), direct comparisons between first-line maintenance therapies must be made with caution. Healthcare professionals must factor individual patient circumstances when choosing the most appropriate therapy.

Budget impact analysis of niraparib for first-line maintenance therapy in advanced ovarian cancer from a US payer perspective.

BACKGROUND: Ovarian cancer (OC) is the fifth leading cause of cancer death in women and has the highest mortality rate of gynecological cancers. Niraparib was recently approved by the FDA for the maintenance treatment of adult patients with advanced epithelial OC in complete or partial response to first-line platinum-based chemotherapy (PBC) regardless of biomarker status. OBJECTIVE: To estimate the direct economic impact on US payers of adding niraparib as a first-line maintenance therapy for patients with advanced OC. METHODS: The model considered 2 scenarios: a current scenario in which niraparib does not have regulatory approval for first-line maintenance therapy and a future scenario in which niraparib has regulatory approval for first-line maintenance therapy. The budget impact was calculated as the difference in cost between the 2 scenarios. The budget impact model (BIM) considered 2 different US health care payer perspectives: a commercial health plan and a Medicare plan. Both payer perspectives were assumed to have a hypothetical 1 million affiliates that were covered. Epidemiological data was used to estimate the eligible incident population of patients with OC. Active surveillance, bevacizumab (as a monotherapy), and olaparib (as a monotherapy restricted to patients with the breast cancer gene [BRCA] mutation) were included in the model as alternative maintenance treatment options (maintenance treatment options required 1% market share for inclusion). Cost categories considered in the BIM included diagnostic testing, treatment acquisition and administration, treatment-emergent adverse events, and subsequent therapy. Results were presented as an incremental budget impact to payers over 3 years. RESULTS: For a commercial health plan of 1 million affiliates, the estimated impact of adding niraparib as a first-line maintenance treatment option for advanced epithelial OC was calculated as $87,906, $93,106, and $87,037 for years 1, 2, and 3, respectively. The average budget impact per member per month was $0.007. For a Medicare health plan of 1 million affiliates, the estimated impact was calculated as $206,785, $219,017, and $204,739 for years 1, 2, and 3, respectively. The average budget impact per member per month was $0.018. One-way sensitivity analyses suggested that budget impact was most sensitive to the treatment duration and market share of niraparib, the non-treatment-specific data on overall survival rates, and the treatment duration of bevacizumab. Treatment of drug-specific adverse events had little impact on the budget model. CONCLUSIONS: The model estimated a minimal budget impact to both a commercial or Medicare health plan following the introduction of niraparib as a first-line maintenance therapy for patients with advanced epithelial OC who are in complete or partial response to first-line PBC regardless of biomarker status. DISCLOSURES: This study was financially supported by GlaxoSmithKline. Liu, Hawkes, Maiese, and Hurteau are employees of GlaxoSmithKline. Travers was employed by GlaxoSmithKline at the time of this study. Spalding and Walder are employees of FIECON Ltd., which was contracted by GlaxoSmithKline to develop the budget impact model used in this study.

Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial.

PURPOSE: This study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer. PATIENTS AND METHODS: Mean progression-free survival (PFS) was estimated for niraparib and RS by fitting parametric survival distributions to Kaplan-Meier data for 553 patients with recurrent ovarian cancer who were enrolled in the phase III ENGOT-OV16/NOVA trial. Patients were categorized according to the presence or absence of a germline BRCA mutation-gBRCAmut and non-gBRCAmut cohorts. Mean time with toxicity was estimated based on the area under the Kaplan-Meier curve for symptomatic grade 2 or greater fatigue, nausea, and vomiting adverse events (AEs). Time with toxicity was the number of days a patient experienced an AE post-random assignment and before disease progression. TWiST was estimated as the difference between mean PFS and time with toxicity. Uncertainty was explored using alternative PFS estimates and considering all symptomatic grade 2 or greater AEs. RESULTS: In the gBRCAmut and non-gBRCAmut cohorts, niraparib treatment resulted in a mean PFS benefit of 3.23 years and 1.44 years, respectively, and a mean time with toxicity of 0.28 years and 0.10 years, respectively, compared with RS. Hence, niraparib treatment resulted in a mean TWiST benefit of 2.95 years and 1.34 years, respectively, compared with RS, which is equivalent to more than four-fold and two-fold increases in mean TWiST between niraparib and RS in the gBRCAmut and non-gBRCAmut cohorts, respectively. This TWiST benefit was consistent across all sensitivity analyses, including modeling PFS over 5-, 10-, and 15-year time horizons. CONCLUSION: Patients who were treated with niraparib compared with RS experienced increased mean TWiST. Thus, patients who were treated with niraparib in the ENGOT-OV16/NOVA trial experienced more time without symptoms or symptomatic toxicities compared with control.

Cost-Effectiveness of Niraparib Versus Routine Surveillance, Olaparib and Rucaparib for the Maintenance Treatment of Patients with Ovarian Cancer in the United States.

OBJECTIVES: The aim was to evaluate the cost-effectiveness of niraparib compared with routine surveillance (RS), olaparib and rucaparib for the maintenance treatment of patients with recurrent ovarian cancer (OC). METHODS: A decision-analytic model estimated the cost per quality-adjusted life-year (QALY) gained for niraparib versus RS, olaparib, and rucaparib from a US payer perspective. The model considered recurrent OC patients with or without germline BRCA mutations (gBRCAmut and non-gBRCAmut), who were responsive to their last platinum-based chemotherapy regimen. Model health states were: progression-free disease, progressed disease and dead. Mean progression-free survival (PFS) was estimated using parametric survival distributions based on ENGOT-OV16/NOVA (niraparib phase III trial), ARIEL3 (rucaparib phase III trial) and Study 19 (olaparib phase II trial). Mean overall survival (OS) benefit was estimated as double the mean PFS benefit based on the relationship between PFS and OS observed in Study 19. Costs included: drug, chemotherapy, monitoring, adverse events, and terminal care. EQ-5D utilities were estimated from trial data. RESULTS: Compared to RS, niraparib was associated with an incremental cost-effectiveness ratio (ICER) of US$68,287/QALY and US$108,287/QALY for gBRCAmut and non-gBRCAmut, respectively. Compared to olaparib and rucaparib, niraparib decreased costs and increased QALYs, with a cost saving of US$8799 and US$22,236 versus olaparib and US$198,708 and US$73,561 versus rucaparib for gBRCAmut and non-gBRCAmut, respectively. CONCLUSIONS: Niraparib was estimated to be less costly and more effective compared to olaparib and rucaparib, and the ICER fell within an acceptable range compared to RS. Therefore, niraparib may be considered a cost-effective maintenance treatment for patients with recurrent OC.