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.

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.

Utility and diagnostic accuracy of fallopian tube touch imprint cytology.

OBJECTIVE: To determine the diagnostic accuracy of cytology smears in distinguishing between tube and non-tube structures. METHODS: One hundred cytology smears of fallopian tube and non-tube structures (vessels, round and ovarian ligaments) were prepared from surgically removed uterus and fallopian tube specimens and stained by the Papanicolaou method. The slides were reviewed blindly by pathologists and interpreted as tube or non-tube structures. The results were compared to the histological examination of the same specimens. FINDINGS: Results indicated an overall accuracy of 97% with a specificity of 98% and sensitivity of 96% for cytology smears, taking histology as the gold standard. Positive and negative predictive values were 96.1% and 97.9%, respectively. CONCLUSION: Cytology smears are a convenient and cost effective tool for laboratory confirmation of tubal sterilization. This method can reduce the costs of laboratory examination, especially in developing countries, where tubal sterilizations are done in large cohorts. However, histological slides remain the gold standard in cases of medicolegal problems.