TA898 · STA
Only if used as first-line treatment of advanced stage cancer and the company provides it according to the commercial arrangement
Source documents
Intervention
Conditions
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| pembrolizumab plus platinum chemotherapy | active drug | Yes | Yes |
| pembrolizumab plus platinum doublet chemotherapy | active drug | — | Yes |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| BRF113928 | single_arm | phase 3 | Yes |
| KEYNOTE-189 | — | — | Yes |
Economic model
ICER
Methodological decisions (12)
Inclusion of BRAF V600 mutation testing costs in cost-effectiveness analysis
Company: Did not include costs as this test is done in routine practice
ERG: Questioned whether BRAF V600 testing was truly routine practice
Committee: Agreed testing is routine practice and costs should not be included, consistent with NICE methodology
ICER impact: negligible
Inclusion of costs for BRAF V600 mutation testing
Company: Did not include genomic testing costs as already done in routine practice
ERG: Questioned whether BRAF V600 testing was truly routine practice
Committee: BRAF V600 mutation testing is routine practice; costs should not be included in line with NICE methodology
ICER impact: decreases
Approach to discounting future costs in the model
Company: Modelled discounting discretely from beginning of second year
ERG: Chose to discount costs continuously
Committee: Not yet determined in pages provided
ICER impact: uncertain_direction
Method of discounting future costs in the economic model
Company: Discrete discounting from beginning of second year, updating discount rate annually
ERG: Continuous discounting from outset, updating discount rate every cycle
Committee: Continuous discounting from outset of model
ICER impact: negligible
Clinical equivalence between dabrafenib plus trametinib and pembrolizumab plus platinum chemotherapy
Company: Presented analysis assuming clinical equivalence as conservative assumption in absence of trial evidence
ERG: Concluded assumption was not supported by evidence and would ignore effects of subsequent treatments
Committee: Not preferred for decision making due to lack of evidence support
ICER impact: uncertain_direction
Choice between MAIC and naive unanchored comparison for BRAF V600 comparator evidence
Company: Used MAIC approach with covariates based on BRF113928 and KEYNOTE-189
ERG: Presented two base cases: one informed by MAIC and one by naive unanchored comparison
Committee: MAIC was acceptable and preferred despite limitations, but committee preferred sensitivity MAIC with fewer covariates to maintain sample size
ICER impact: uncertain_direction
Use of MAIC to compare dabrafenib plus trametinib (from BRF113928) with pembrolizumab plus platinum chemotherapy (from KEYNOTE-189)
Company: Base-case MAIC adjusted for covariates found to be statistically significantly associated with PFS or OS, plus covariates used in previous NICE appraisals
ERG: Agreed base-case MAIC was acceptable despite limitations
Committee: Preferred the sensitivity MAIC with larger effective sample size and less uncertain effect estimates, avoiding covariates from previous appraisals
ICER impact: uncertain_direction
Generalisability of KEYNOTE-189 evidence to BRAF V600 population
Company: KEYNOTE-189 participants would have been eligible for BRF113928, making it suitable for comparator efficacy
ERG: Questioned whether KEYNOTE-189 results were generalisable since it did not collect BRAF mutation status and most participants would not have BRAF V600
Committee: Accepted KEYNOTE-189 as preferred evidence source for comparator efficacy despite lack of BRAF V600-specific data
ICER impact: uncertain_direction
Assumption regarding adhere to oral therapies and impact on efficacy
Company: Non-adherence effects included via trial effect on PFS and OS; cost calculations account for relative dose intensity
ERG: Noted possible drawbacks to oral therapies such as non-adherence with unmodelled negative effect on efficacy
Committee: Any non-adherence adequately accounted for in cost-effectiveness modelling
ICER impact: negligible
Consideration of second-line use of dabrafenib plus trametinib
Company: Most people with BRAF V600-mutated NSCLC would receive dabrafenib plus trametinib first line; second-line population small and declining due to testing delays being resolved
ERG: Noted sample size in second-line analysis was very small and cohort had previous chemotherapy not immunochemotherapy; effectiveness when used second line was uncertain
Committee: Second-line population likely to fall substantially; unable to consider cost-effectiveness for previously treated NSCLC due to absence of evidence
ICER impact: uncertain_direction
Source of health-state utility values
Company: Health state utilities from NICE's technology appraisal guidance on pralsetinib; adverse event disutilities from tepotinib guidance
ERG: Same source approach
Committee: Acceptable as in line with other similar appraisals in disease area
ICER impact: uncertain_direction
Modelling intravenous disutility for pembrolizumab plus platinum chemotherapy
Company: Modelled disutility decrement of 0.023 per cycle for IV infusion, later modified to only incur in cycles where IV infusion occurred
ERG: Did not include disutility decrement in base case; considered the value too high compared to other health states, obtained via non-reference case method
Committee: Did not explicitly model disutility in base case, but would consider as potentially uncaptured health benefit; noted plausibility but difficulty in quantification
ICER impact: uncertain_direction
Evidence gaps
Commercial arrangement
Special considerations