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Olaparib for Maintenance Treatment of BRCA 1 or 2 Mutated, Relapsed, Platinum-Sensitive Ovarian, Fallopian Tube and Peritoneal Cancer in People Whose Relapsed Disease has Responded to Platinum-Based Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of olaparib (AstraZeneca) to submit evidence on the clinical and cost effectiveness of olaparib for the maintenance treatment of BRCA1/2 mutated (BRCAm), platinum-sensitive relapsed (PSR) ovarian, fallopian tube and peritoneal cancer in people whose relapsed disease has responded to platinum-based chemotherapy. The Evidence Review Group (ERG) produced a critical review of the evidence contained within the company’s submission (CS) to NICE. The clinical evidence related to one phase II, double-blind randomised controlled trial that recruited 265 patients with PSR serous ovarian cancer (OC) regardless of BRCAm status. Patients received olaparib 400 mg twice daily (b.i.d.) or matched placebo. In the whole population, the primary endpoint of progression-free survival (PFS) was met (hazard ratio [HR] 0.35; 95 % confidence interval [CI] 0.25–0.49, p < 0.01) for olaparib versus placebo. The BRCAm subgroup analysis (added after the study commenced but 1 month before the primary analysis was undertaken) reported an HR for PFS of 0.18 (95 % CI 0.10–0.31, p < 0.0001) for olaparib versus placebo, though interaction tests appeared inconclusive. Overall survival was not statistically significant in the whole group (HR 0.88; 95 % CI 0.64–1.21; p = 0.44) or the BRCAm subgroup (0.73; 95 % CI 0.45–1.17; p = 0.19), though treatment switching may have confounded results. The exclusion of data from sites allowing crossover resulted in an HR for overall survival (OS) of 0.52 (95 % CI 0.28–0.97, p = 0.039) in the BRCAm group. Health-related quality-of-life measures were not significantly different between groups. All post hoc exploratory outcomes (time to treatment discontinuation/death, time to first subsequent therapy/death, and time to second subsequent therapy/death) were statistically significantly better in the olaparib arm in the whole population and the BRCAm subgroup analyses. Adverse events were more frequent for olaparib but were largely minor or manageable. The company’s semi-Markov model assessed the cost effectiveness of olaparib versus routine surveillance in patients with BRCAm PSR OC from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a lifetime horizon. The model suggests that the incremental cost-effectiveness ratio (ICER) for olaparib versus routine surveillance is expected to be approximately £49,146 per quality-adjusted life-year (QALY) gained. The ERG did not consider the company’s cost-effectiveness estimates to be credible. Additional ERG analyses suggested that the ICER is likely to be more than £92,214 per QALY gained. Additional analyses provided by the company in patients who received three or more lines of chemotherapy suggested a more favourable cost-effectiveness profile for olaparib. The NICE Appraisal Committee recommended olaparib for this subgroup provided the cost of olaparib for people who continue to receive treatment after 15 months will be met by the company.

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Acknowledgments

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (Project No. 14/57/01). See the HTA programme website for further project information (http://www.hta.ac.uk). This summary of the ERG report was compiled after NICE issued the FAD. All authors have commented on the submitted manuscript and have given their approval for the final version to be published. The views expressed in this report are those of the authors and not necessarily those of the NIHR HTA Programme. Any errors are the responsibility of the authors.

Author contributions

Sue Harnan summarised and critiqued the clinical-effectiveness data reported within the CS. Ruth Wong critiqued the company’s search strategy. Shijie Ren critiqued the statistical analyses undertaken by the company. Clara Mukuria advised on the company’s use of health utility mapping. Paul Tappenden and Praveen Thokala critiqued the health economic analysis submitted by the company. Paul Tappenden and Shijie Ren undertook the ERG’s exploratory analyses. Clare Green, Simon Pledge and John Tidy provided clinical advice to the ERG throughout the project. All authors were involved in drafting and commenting on the final report. Paul Tappenden acts as the guarantor of the manuscript.

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Paul Tappenden, Sue Harnan, Shijie Ren, Praveen Thokala, Ruth Wong, Clara Mukuria, Clare Green, Simon Pledge and John Tidy declare no financial conflicts of interest.

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Tappenden, P., Harnan, S., Ren, S. et al. Olaparib for Maintenance Treatment of BRCA 1 or 2 Mutated, Relapsed, Platinum-Sensitive Ovarian, Fallopian Tube and Peritoneal Cancer in People Whose Relapsed Disease has Responded to Platinum-Based Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. PharmacoEconomics 35, 97–109 (2017). https://doi.org/10.1007/s40273-016-0440-x

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Keywords

  • Overall Survival
  • National Health Service
  • Evidence Review Group
  • Routine Surveillance
  • Interactive Voice Response System