Treatment options for patients with metastatic Merkel cell carcinoma (mMCC) are severely limited, and survival for patients with mMCC is poor with existing, unlicensed palliative chemotherapy regimens and best supportive care. |
Avelumab may provide a cost-effective option for treatment-experienced mMCC patients and, while data are still maturing, demonstrates promising outcomes in treatment-naïve mMCC patients. |
1 Introduction
2 Methods
2.1 Model Overview
2.2 Clinical Model Parameters
2.2.1 Comparator Treatments
2.2.2 Survival Outcomes for Comparator Treatments
2.2.3 Survival Outcomes for Avelumab
2.2.4 Adverse Events
2.2.5 Health-Related Quality of Life
2.3 Cost Model Parameters
2.3.1 Treatment Costs
2.3.2 Medical Resource Use
2.4 Clinical and External Validation
2.5 Analysis
3 Results
3.1 Base-Case Results
Treatment | Total | Incremental (vs. avelumab) | ICER (£) | ||||
---|---|---|---|---|---|---|---|
Costs (£) | LYs | QALYs | Costs (£) | LYs | QALYs | ||
TE mMCC
| |||||||
Chemotherapy | 9834 | 0.41 | 0.30 | 78,395 | 3.74 | 2.30 | 34,113 |
SC | 7584 | 0.41 | 0.31 | 80,646 | 3.74 | 2.29 | 35,274 |
BSC | 7465 | 0.41 | 0.31 | 80,764 | 3.74 | 2.29 | 35,335 |
Avelumab | 88,229 | 4.15 | 2.60 | ||||
TN mMCC
| |||||||
Chemotherapy | 10,607 | 1.94 | 1.34 | 77,292 | 3.56 | 2.02 | 38,205 |
SC | 8918 | 1.94 | 1.35 | 78,981 | 3.56 | 2.02 | 39,178 |
BSC | 7229 | 1.94 | 1.36 | 80,669 | 3.56 | 2.01 | 40,158 |
Avelumab | 87,899 | 5.50 | 3.37 |
3.2 Probabilistic Sensitivity Analysis
Pairwise cost-effectiveness results | |||||||
---|---|---|---|---|---|---|---|
Treatment | Total | Incremental (vs. avelumab) | ICER (£) | ||||
Costs (£) | LYs | QALYs | Costs (£) | LYs | QALYs | ||
TE mMCC
| |||||||
Chemotherapy | 9838 | 0.41 | 0.30 | 80,143 | 3.84 | 2.35 | 34,076 |
SC | 7591 | 0.41 | 0.31 | 82,390 | 3.84 | 2.34 | 35,208 |
BSC | 7473 | 0.41 | 0.31 | 82,508 | 3.84 | 2.34 | 35,268 |
Avelumab | 89,981 | 4.26 | 2.65 | ||||
TN mMCC
| |||||||
Chemotherapy | 10,622 | 1.95 | 1.35 | 80,573 | 3.64 | 2.07 | 38,986 |
SC | 8929 | 1.95 | 1.36 | 82,266 | 3.64 | 2.06 | 39,943 |
BSC | 7236 | 1.95 | 1.37 | 83,959 | 3.64 | 2.05 | 40,907 |
Avelumab | 91,194 | 5.60 | 3.42 |
Parameter | Value | Lower 95% CI | Upper 95% CI | Distribution | Source or justification |
---|---|---|---|---|---|
Discount rate, costs | 3.50% | NA | NA | Varied in scenario analysis | NICE reference case [59] |
Discount rate, QALYs | 3.50% | NA | NA | Varied in scenario analysis | |
Discount rate, LYs | 0.00% | NA | NA | Varied in scenario analysis | |
Model cycle length | 1 week | NA | NA | Not varied | Structural assumption |
Model time horizon | 40 years | NA | NA | Not varied | NICE reference case [59] |
HR: improvement in OS for avelumab (TN vs. TE) | 0.800 | 0.655 | 0.968 | Log-normal | Assumptions validated by clinical expert opinion |
HR: improvement in PFS for avelumab (TN vs. TE) | 1.000 | 0.818 | 1.210 | Log-normal | |
RDI: avelumab | 95.43% | 93.59% | 97.27% | Normal | JAVELIN Merkel 200 [7] |
RDI: chemotherapy | 66.67% | 53.60% | 79.73% | Normal | Clinical validation |
Utility, progression-free, (-5L) | 0.827 | 0.783 | 0.867 | Beta | Kaufman et al. [39] |
Utility, post-progression (-5L) | 0.742 | 0.690 | 0.790 | Beta | |
Utility, > 100 days to death (-3L) | 0.774 | 0.734 | 0.813 | Beta | NICE TA517 [55] |
Utility, 30–100 days to death (-3L) | − 0.020 | 0.000 | − 0.108 | Beta | |
Utility, < 30 days to death (-3L) | − 0.066 | − 0.020 | − 0.138 | Beta | |
Administration cost, IV drugs | £199.00 | £198.81 | £199.19 | Normal | |
Cost, GP visit | £36.00 | £28.94 | £43.06 | Normal | |
Cost, CT scan | £120.99 | £120.95 | £121.03 | Normal | |
Cost, FBC | £3.00 | £3.00 | £3.00 | Normal | |
Cost, LFT | £1.00 | £0.80 | £1.20 | Normal | |
Cost, RFT | £1.00 | £0.80 | £1.20 | Normal | |
Cost, TFT | £1.00 | £0.80 | £1.20 | Normal | |
Cost, radiotherapy | £126.60 | £126.58 | £126.62 | Normal | |
Cost, EoL, health care | £4867.53 | £3913.51 | £5821.55 | Normal | Round et al. [54] |
Cost, EoL, social care | £2151.59 | £1729.89 | £2573.29 | Normal | |
MRU frequency, GP visit, avelumab, PF | 0.250 | 0.201 | 0.299 | Normal | Assumptions validated by clinical expert opinion |
MRU frequency, CT scan, avelumab, PF | 0.077 | 0.062 | 0.092 | Normal | |
MRU frequency, FBC, avelumab, PF | 0.500 | 0.402 | 0.598 | Normal | |
MRU frequency, LFT, avelumab, PF | 0.500 | 0.402 | 0.598 | Normal | |
MRU frequency, RFT, avelumab, PF | 0.500 | 0.402 | 0.598 | Normal | |
MRU frequency, TFT, avelumab, PF | 0.500 | 0.402 | 0.598 | Normal | |
MRU frequency, radiotherapy, avelumab, PF | 0.000 | 0.000 | 0.000 | Normal | |
MRU frequency, GP visit, chemotherapy, PF | 0.333 | 0.268 | 0.399 | Normal | |
MRU frequency, CT scan, chemotherapy, PF | 0.115 | 0.093 | 0.138 | Normal | |
MRU frequency, FBC, chemotherapy, PF | 0.333 | 0.268 | 0.399 | Normal | |
MRU frequency, LFT, chemotherapy, PF | 0.333 | 0.268 | 0.399 | Normal | |
MRU frequency, RFT, chemotherapy, PF | 0.333 | 0.268 | 0.399 | Normal | |
MRU frequency, TFT, chemotherapy, PF | 0.000 | 0.000 | 0.000 | Normal | |
MRU frequency, radiotherapy, chemotherapy, PF | 0.000 | 0.000 | 0.000 | Normal | |
Drug cost, avelumab | £768.00 | NA | NA | Not varied | BNF online [46] |
Drug cost, carboplatin | £25.25 | £25.18 | £25.32 | Normal | eMIT [60] |
Drug cost, etoposide IV | £24.96 | £22.16 | £27.76 | Normal | eMIT [60] |
Drug cost, etoposide oral | £87.23 | NA | NA | Not varied | BNF online [46] |
Drug cost, cisplatin | £10.56 | £10.49 | £10.63 | Normal | eMIT [60] |
AE probability, lymphopenia, avelumab | 2.27% | Beta | JAVELIN Merkel 200 [7] | ||
AE probability, anaemia, carboplatin + etoposide | 7.38% | Beta | Socinski et al. [36] | ||
AE probability, fatigue, carboplatin + etoposide | 3.13% | Beta | |||
AE probability, febrile neutropenia, carboplatin + etoposide | 4.47% | Beta | |||
AE probability, hyponatraemia, carboplatin + etoposide | 1.12% | Beta | |||
AE probability, leukopenia, carboplatin + etoposide | 8.28% | Beta | |||
AE probability, nausea/vomiting, carboplatin + etoposide | 0.90% | Beta | |||
AE probability, neutropenia, carboplatin + etoposide | 46.98% | Beta | |||
AE probability, thrombocytopenia, carboplatin + etoposide | 10.29% | Beta | |||
AE probability, hair loss, carboplatin + etoposide | 34.00% | Beta | |||
AE probability, anaemia, cisplatin + etoposide | 6.67% | Beta | Sun et al. [37] | ||
AE probability, low haemoglobin, cisplatin + etoposide | 5.33% | Beta | |||
AE probability, leukopenia, cisplatin + etoposide | 19.33% | Beta | |||
AE probability, nausea/vomiting, cisplatin + etoposide | 6.70% | Beta | |||
AE probability, neutropenia, cisplatin + etoposide | 44.00% | Beta | |||
AE probability, thrombocytopenia, cisplatin + etoposide | 7.33% | Beta | |||
AE probability, hair loss, cisplatin + etoposide | 13.33% | Beta | |||
AE cost, anaemia | £799.39 | £657.09 | £977.46 | Normal | |
AE cost, fatigue | £66.45 | £53.43 | £79.47 | Normal | |
AE cost, febrile neutropenia | £4543.44 | £3652.94 | £5433.93 | Normal | |
AE cost, low haemoglobin | £66.45 | £53.43 | £79.47 | Normal | |
AE cost, hyponatraemia | £66.45 | £53.43 | £79.47 | Normal | |
AE cost, leukopenia | £281.67 | £226.46 | £336.88 | Normal | |
AE cost, lymphopenia | £281.67 | £226.46 | £336.88 | Normal | |
AE cost, nausea/vomiting | £218.27 | £181.41 | £269.86 | Normal | |
AE cost, neutropenia | £281.67 | £226.46 | £336.88 | Normal | |
AE cost, thrombocytopenia | £286.12 | £230.05 | £342.20 | Normal | |
AE cost, hair loss | £0.00 | £0.00 | £0.00 | Normal | |
AE disutility, anaemia | − 0.090 | − 0.055 | − 0.133 | Beta | |
AE disutility, fatigue | − 0.073 | − 0.041 | − 0.114 | Beta | |
AE disutility, febrile neutropenia | − 0.090 | − 0.061 | − 0.124 | Beta | |
AE disutility, low haemoglobin | − 0.080 | − 0.052 | − 0.114 | Beta | |
AE disutility, hyponatraemia | − 0.090 | − 0.062 | − 0.122 | Beta | |
AE disutility, leukopenia | − 0.090 | − 0.062 | − 0.122 | Beta | |
AE disutility, lymphopenia | − 0.090 | − 0.062 | − 0.122 | Beta | |
AE disutility, nausea/vomiting | − 0.048 | − 0.022 | − 0.084 | Beta | |
AE disutility, neutropenia | − 0.090 | − 0.062 | − 0.122 | Beta | |
AE disutility, thrombocytopenia | − 0.108 | − 0.089 | − 0.128 | Beta | |
AE disutility, hair loss | − 0.045 | − 0.021 | − 0.078 | Beta | |
AE duration, anaemia | 21 days | 17 days | 25 days | Normal | Assumptions validated by clinical expert opinion |
AE duration, fatigue | 21 days | 17 days | 25 days | Normal | |
AE duration, febrile neutropenia | 4 days | 3 days | 5 days | Normal | |
AE duration, low haemoglobin | 21 days | 17 days | 25 days | Normal | |
AE duration, hyponatraemia | 2 days | 2 days | 2 days | Normal | |
AE duration, leukopenia | 2 days | 2 days | 2 days | Normal | |
AE duration, lymphopenia | 2 days | 2 days | 2 days | Normal | |
AE duration, nausea/vomiting | 3 days | 2 days | 4 days | Normal | |
AE duration, neutropenia | 2 days | 2 days | 2 days | Normal | |
AE duration, thrombocytopenia | 24 days | 19 days | 28 days | Normal | |
AE duration, hair loss | 21 days | 17 days | 25 days | Normal |