title: 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.
authors: ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, England, UK. p.tappenden@sheffield.ac.uk.
authors: Paul
authors: 0000-0001-6612-2332
authors: P
authors: Tappenden
authors: ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, England, UK.
authors: Sue
authors: S
authors: Harnan
authors: ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, England, UK.
authors: Shijie
authors: S
authors: Ren
authors: ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, England, UK.
authors: Praveen
authors: P
authors: Thokala
authors: ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, England, UK.
authors: Ruth
authors: R
authors: Wong
authors: ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, England, UK.
authors: Clara
authors: C
authors: Mukuria
authors: Southampton General Hospital and Hampshire Hospitals Foundation Trust, Southampton, UK.
authors: Clare
authors: C
authors: Green
authors: Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors: Simon
authors: S
authors: Pledge
authors: Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors: John
authors: J
authors: Tidy
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D003362:Cost-Benefit Analysis; D018572:Disease-Free Survival; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000191:economics / Q000473:pathology; D005260:Female; D006801:Humans; D008390:Markov Chains; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000191:economics / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000191:economics / Q000473:pathology; D010793:Phthalazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D013673:Technology Assessment, Biomedical / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D010793:Phthalazines; D010879:Piperazines; C531550:olaparib