TA962 · STA
Recommended only if the conditions in the managed access agreement for olaparib are followed. FIGO stages 3 and 4 only. BRCA mutation-positive (germline and/or somatic). Treatment continued until radiological disease progression, unacceptable toxicity, or for up to 2 years if no radiological evidence of disease.
Source documents
Intervention
Conditions
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| placebo | placebo | — | — |
| routine surveillance | standard of care | Yes | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| SOLO-1 | RCT | III | Yes |
| Study 19 | RCT | — | — |
| GOG-172 | RCT | — | — |
| JGOG-3016 | RCT | — | — |
Economic model
ICER
Methodological decisions (13)
Price per tablet of olaparib is the same regardless of dose, so cost of treatment per day for reduced dose is same as full dose. Economic modelling should use cost of whole tablets rather than average cost per milligram.
Committee: use cost of whole tablets
ICER impact: negligible
Price per tablet is same regardless of dose, so reduced-dose cost equals full-dose cost. After technical engagement, modelling revised to use cost of whole tablets rather than average cost per milligram.
Company: Initially used average cost per milligram; revised to whole tablets after TE
Committee: Use whole tablet costs
ICER impact: increases
Company's model assumes approximately 20% of people are cured from ovarian cancer. Clinical experts explained this is plausible (Study 19 shows 10% disease-free after 10 years, termed 'super responders' more likely from complete responses), but no OS benefit yet demonstrated in SOLO-1.
Company: 20% cure assumption is plausible and should be included
Committee: Cure is possible and estimate is plausible, but uncertainties remain without OS benefit demonstration in SOLO-1
ICER impact: increases
Olaparib for first-line maintenance treatment does not meet criteria for 1.5% discount rates. Reference case 3.5% discount rates should be applied in cost-effectiveness analyses.
Committee: 3.5% discount rates
ICER impact: increases
Company presented a partitioned survival model with 3 health states (progression-free, progressed disease and death). ERG commented on model structure limitations.
Company: 3-state partitioned survival model
ERG: raised limitations with model structure
Committee: 3-state partitioned survival model acceptable for decision making
ICER impact: negligible
Company submitted 4-health state partitioned survival model with PFS-2 state. ERG considered 3-state model oversimplified and suggested sequenced model would be more appropriate, but acknowledged lack of data to populate multiple therapy lines.
Company: 4-health state partitioned survival model with PFS-2 is appropriate
ERG: Sequenced model would be more appropriate but lacks data; 3-state model was oversimplified
Committee: 4-state model is acceptable for decision making, though main limitations (immature OS data, complexity of pathway) would persist with any model structure
ICER impact: uncertain_direction
Committee noted 82% of SOLO-1 had complete response to platinum chemotherapy, but estimates NHS percentage at ~70% of responders. Clinical experts indicated complete response patients likely to have better long-term outcomes. Additionally, Edinburgh OvCa Database lacks information on response type, limiting comparability.
Company: 82% complete response rate in SOLO-1 is representative
Committee: NHS proportion of complete responders estimated at 70%, lower than trial's 82%. People with residual disease expected to have worse outcomes.
ICER impact: increases
Treatment with olaparib should be stopped after 2 years unless there is evidence of residual disease. Committee considered approximately 15% of patients would continue beyond 2 years due to residual disease, though this estimate is uncertain and may be optimistic.
Committee: approximately 15% continue beyond 2 years
ICER impact: increases
Uncertainty about percentage of patients eligible to continue olaparib beyond 2 years (if residual disease and meet continuation criteria). Committee estimated ~15% vs company's 10%, with large impact on treatment costs.
Company: Approximately 10% of patients eligible to continue beyond 2 years
Committee: Approximately 15% could continue in UK clinical practice, though this estimate may be optimistic due to worse UK outcomes
ICER impact: decreases
Company used PFS-2 as surrogate for OS in modelling, predicting 20% survival difference at 20 years. However, SOLO-1 shows OS curve convergence at ~40 months, unlike expectations. Committee noted this is a major weakness; model does not reflect trial's interim OS results.
Company: PFS-2 is appropriate surrogate; immature OS data would give unrealistic routine surveillance OS estimates. Model predicts OS gains will emerge with longer follow-up, consistent with Study 19 pattern.
ERG: Not explicitly stated but concerned model uses extrapolated PFS-2, not trial OS data
Committee: OS modelling is very uncertain and may overestimate survival gain; not possible to resolve until more mature OS data available from SOLO-1
ICER impact: increases
Committee discussed uncertainty about how long olaparib treatment benefit will extend, particularly given convergence of OS curves at early SOLO-1 data cuts. Linked to immature OS evidence.
Company: Treatment benefit expected to persist based on Study 19 pattern and achieved PFS gains
Committee: Duration uncertain; cannot assume early curve convergence will reverse with longer follow-up
ICER impact: uncertain_direction
Whether progression-free survival benefit from olaparib will translate into overall-survival benefit. Study 19 shows similar pattern of convergence after 37 months, then OS benefit observed after 78 months. Relationship may be 1:1 (Sundar et al.) or 1:2 or more (GOG-172, JGOG-3016).
Committee: expected that treatment with olaparib will extend life but extent is uncertain
ICER impact: uncertain_direction
Uncertainty about use of PARP inhibitors after second-line platinum-based chemotherapy and about retreatment with PARP inhibitor. SOLO-1 had subsequent PARP inhibitor use in both arms; committee noted uncertainty about whether trial reflects UK practice.
Company: Subsequent PARP inhibitor use in SOLO-1 is reasonable reflection of UK clinical practice
Committee: There is uncertainty around use of PARP inhibitors after second-line therapy; this has large impact on cost-effectiveness
ICER impact: uncertain_direction
Evidence gaps
Commercial arrangement
Special considerations
Cross-references