TABLE 1.
Summary of Model Inputs
| Input | Rib + Let | Let Monotherapy | Pal + Let | Reference |
|---|---|---|---|---|
| Survival | ||||
| PFS, HR, mean (95% CI)a | – | – | 0.560 (0.460-0.680) | Data on fileb |
| OS, HR, mean (95% CI)a | 0.840 (0.492-1.345) | 0.840 (0.492-1.345) | ||
| OvR, OR, mean (95% CI)a | 1.807 (1.320-2.520) | 1.400 (1.040-1.890) | ||
| HRs | ||||
| PFS | 1.010 (0.730-1.390)c | – | – | Data on fileb |
| Drug acquisition costs per month, $ | ||||
| CDK 4/6 inhibitor | 600 mg: 10,950 | – | 10,963 | 18, data on filee |
| 400 mg: 8,760 | ||||
| 200 mg: 4,380d | ||||
| Letrozole | 8f | 8f | 8f | 18 |
| PF | PD | |||
| Disease management costs per month, $ | ||||
| Outpatient visit | 47 | 214 | 17, 20 | |
| Bone metastases management | 160 | 342 | ||
| Hospitalization | 272 | 703 | ||
| Monitoring (LFT, CBC, and CMP) | 15 | – | ||
| Laboratory scan and tests | – | 420 | ||
| Bone scan | 54 | – | ||
| CT scan | 139 | – | ||
| Palliative care | – | 4,521 | ||
| Rib + Let | Let Monotherapy | Pal + Let | ||
| Add-on treatment costs, $ | ||||
| Monitoring at treatment initiation | 138 | – | 42 | 37, 38, data on fileg |
| Monthly monitoring | 22 | – | 11 | |
| End-of-life costs, $ | 2,392 | 20, data on fileg | ||
| AEs, probability, % | ||||
| Diarrhea | 1.2 | 0.9 | 1.7 | 6-8 |
| Fatigue | 2.4 | 0.9 | 2.3 | |
| Infection | 4.2 | 2.4 | 4.4 | |
| Nausea | 2.4 | 0.6 | 0.6 | |
| Febrile neutropenia | 1.2 | 0.0 | 0.4 | |
| Pulmonary embolism | 0.0 | 0.3 | 5.0 | |
| Vomiting | 3.6 | 0.9 | 0.4 | |
| Anemia | 1.2 | 1.2 | 5.5 | |
| AEs, unit cost, $ | ||||
| Diarrhea | 7,377 | 17, 24, 39 | ||
| Fatigue | 6,908 | |||
| Infection | 10,128 | |||
| Nausea | 6,182 | |||
| Febrile neutropenia | 21,156 | |||
| Pulmonary embolism | 10,036 | |||
| Vomiting | 5,246 | |||
| Anemia | 6,777 | |||
| Health-state utility values, mean (SE) | ||||
| PFS | Data on fileg 26 | |||
| CR/PR | 0.837 (0.007) | |||
| Stable disease | 0.830 (0.006) | |||
| PD | 0.443h | |||
| AE disutility valuesi | ||||
| Diarrhea | -0.060 | 6 | ||
| Fatigue | -0.029 | |||
| Infection | -0.050 | |||
| Nausea | -0.021 | |||
| Febrile neutropenia | -0.012 | |||
| Pulmonary embolism | -0.050 | |||
| Vomiting | -0.050 | |||
| Anemia | -0.029 | |||
| Discounting rate, % | 3.000 | 28 | ||
aVersus letrozole monotherapy.
bData on file, Analysis Group, Systematic literature review and network meta-analysis of clinical trials in the first-line setting for advanced HR+/HER2- breast cancer, 2017.
cVersus palbociclib plus letrozole; used as a surrogate outcome to generate time-to-treatment discontinuation for palbociclib plus letrozole.
dThe model estimates the number of patients on each dose over time using data from MONALEESA-2. This is modeled using the distribution of doses received and the median time to dose reduction during MONALEESA-2. All patients initiate therapy at the 600 mg dose. Between month 0 and the median time to reduction (5.0 months in the base case), the proportion of patients at the 400 mg or 200 mg doses increases at a linear rate. After the median time to reduction, the dose distribution is held constant until the end of the time horizon.
eData on file, Novartis, e-mail communications, 2016.
fWAC price of $8; however, with a copayment of $11, the acquisition cost is reduced to $0.
gData on file, Novartis, Clinical study report: a randomized double-blind, placebo controlled study of LEE011 in combination with letrozole for the treatment of postmenopausal women with hormone receptor positive, HER2-negative, advanced breast cancer who received no prior therapy for advanced disease, 2016.
hStandard error was not reported by Lloyd et al. (2006);26 the model assumes that the standard error is equivalent to 10% of the mean utility.
iA duration of 30 days was applied in each case.
AE = adverse event; CBC = complete blood count; CDK 4/6 = cyclin-dependent kinase 4 and 6; CI = confidence interval; CMP = comprehensive metabolic panel; CR = complete response; CT = computerized tomography; HR = hazard ratio; Let = letrozole; LFT = liver function test; OR = odds ratio; OS = overall survival; OvR = overall response; Pal = palbociclib; PD = progressed disease; PF = progression free; PFS = progression-free survival; PR = partial response; Rib = ribociclib; SE = standard error.