Trilaciclib and the economic value of multilineage myeloprotection from chemotherapy-induced myelosuppression among patients with extensive-stage small cell lung cancer treated with first-line chemotherapy

Figures & data

Figure 1. Trilaciclib transiently arrests the cell cycle of HSPCs in the presence of chemotherapy to reduce the incidence of chemotherapy-induced myelosuppression. Abbreviations. CDK4/6, cyclin-dependent kinase 4 and 6; HSPC, hematopoietic stem and progenitor cell.

Table 1. Main parameters of the economic evaluation.

Parameter	Choice
Type of analysis	Trial-based CEA
Perspective	Payers
Patient population	ES-SCLC, first line chemotherapy (consistent with pivotal Phase II G1T28-05 trial)
Time horizon	12 weeks (consistent with pivotal G1T28-05 trial duration)
Discount rate	No discount on costs and benefits given the short time horizon
Reference and comparator	Reference: E/P/A Comparator: trilaciclib prior to E/P/A (consistent with pivotal G1T28-05 trial)
Outcomes	Incremental cost, AEs avoided, incremental QALY, incremental cost-effectiveness ratio
Currency	2021 USD (all costs were adjusted for inflation to 2021 USD using the medical care component of the Consumer Price Index)

Abbreviations. AE, adverse event; CEA, cost-effectiveness analysis; E/P/A, carboplatin, etoposide and atezolizumab; ES-SCLC, extensive-stage small cell lung cancer; QALY, quality-adjusted life year; USD, United States dollars.

Table 2. Model parameters and assumptions.

Parameter	Base-case estimate	One-way sensitivity analysis^c		Probabilistic sensitivity analysis					Reference
		Low	High	Distribution	Mean	SE	Alpha	Beta
AE rate,^a %
Trilaciclib prior to E/P/A
Neutropenia	21%	2 approaches: (1) AE rate −5% for both treatment strategies; (2) keep AE rate for E/P/A the same, apply −5% on RRR associated with trilaciclib	2 approaches: (1) AE rate + 5% for both treatment strategies; (2) keep AE rate for E/P/A the same, apply + 5% on RRR associated with trilaciclib	Normal^d	0.212	0.021	NA	NA	Daniel 2020^15
Febrile neutropenia	2%			Normal	0.019	0.002	NA	NA	Daniel 2020^15
Anemia	17%			Normal	0.173	0.017	NA	NA	Daniel 2020^15
Thrombocytopenia	2%			Normal	0.019	0.002	NA	NA	Daniel 2020^15
E/P/A
Neutropenia	60%			Normal	0.604	0.0604	NA	NA	Daniel 2020^15
Febrile neutropenia	6%			Normal	0.057	0.0057	NA	NA	Daniel 2020^15
Anemia	30%			Normal	0.302	0.0302	NA	NA	Daniel 2020^15
Thrombocytopenia	38%			Normal	0.377	0.0377	NA	NA	Daniel 2020^15
AE frequency,^b n
Trilaciclib prior to E/P/A
Neutropenia	1.3	2 approaches: (1) AE frequency −5% for both treatment strategies; (2) keep AE frequency for E/P/A the same, apply −5% on RRR associated with trilaciclib	2 approaches: (1) AE frequency + 5% for both treatment strategies; (2) keep AE frequency for E/P/A the same, apply +5% on RRR associated with trilaciclib	Normal	1.333	0.133	NA	NA	Weiss 2019^14 and Daniel 2020^15
Febrile neutropenia	1.0			Normal	1	0.1	NA	NA	Weiss 2019^14 and Daniel 2020^15
Anemia	1.5			Normal	1.545	0.155	NA	NA	Weiss 2019^14 and Daniel 2020^15
Thrombocytopenia	1.5			Normal	1.5	0.15	NA	NA	Weiss 2019^14 and Daniel 2020^15
E/P/A
Neutropenia	2.5			Normal	2.544	0.254	NA	NA	Weiss 2019^14 and Daniel 2020^15
Febrile neutropenia	1.3			Normal	1.333	0.133	NA	NA	Weiss 2019^14 and Daniel 2020^15
Anemia	1.6			Normal	1.565	0.157	NA	NA	Weiss 2019^14 and Daniel 2020^15
Thrombocytopenia	1.7			Normal	1.739	0.174	NA	NA	Weiss 2019^14 and Daniel 2020^15
Inputs related to prophylactic G-CSF use
Proportion of patients with prophylactic  use of G-CSF without trilaciclib, %	26%								Market research
Reduction in prophylactic G-CSF use  with trilaciclib, %	50%	0%	100%						Weiss 2021^19^e
Average G-CSF cost per cycle, $	$5,733			Gamma	5,733	573	100	57.3	Drugs.com^20 and Eldar-Lissai 2008^21
Average number of prophylactic  G-CSF cycles	3.41								Naeim 2013^22
AE management cost, $
Neutropenia	$21,089	Base-case estimate −10%	Base-case estimate +10%	Gamma	21,089	2,109	100	210.9	Wong 2018^10
Febrile neutropenia	$22,563			Gamma	22,563	2,256	100	225.6	Weycker 2015^23
Anemia	$24,868			Gamma	24,868	2,487	100	248.7	Wong 2018^10
Thrombocytopenia	$27,860			Gamma	27,860	2,786	100	278.6	Wong 2018^10
Treatment cost, $
E/P/A, cost per regimen	$49,537			Gamma	49,537	4,954	100	495.4
Trilaciclib, cost per dose	$2,834	Base-case estimate −10%	Base-case estimate +10%	Gamma	2,834	283	100	28.3	IBM Red Book^24
Utility inputs
E/P/A	0.63			Beta	0.63	0.09	17.66	9.51	Teckle 2013^25, Daniel 2020^15 and post-hoc analysis of G1T28-05 trial data
Trilaciclib prior to E/P/A	0.65			Beta	0.65	0.10	15.54	9.13	Teckle 2013^25, Daniel 2020^15 and post-hoc analysis of G1T28-05 trial data

^aEvent rates are the percentage of patients who experienced at least one grade 3/4 AE in the pivotal Phase II G1T28-05 trial [15]. ^bAE frequency is based on the total number of events divided by the number of patients ≥1 event and represents the weighted average of the pooled data from the G1T28-05 and G1T28-02 trials [14,15]. ^cOne-way sensitivity analyses were conducted by systematically varying one parameter at a time, with the same variation in underlying AE event rate and episode frequency applied to both trilaciclib prior to E/P/A and E/P/A, or with the variation applied only to the RRR associated with trilaciclib. ^dRandomized value was capped between 0 and 1, so that randomization did not provide negative values or values greater than 1 for PSA. ^e50% reduction in the use of prophylactic G-CSF assumed from pooled data analysis from the G1T28-05, G1T28-02 and G1T28-03 trials [19] showing a 50% reduction in the use of any G-CSF.

Abbreviations. AE, adverse event; E/P/A, etoposide, carboplatin and atezolizumab; G-CSF, granulocyte colony-stimulating factor; NA, not applicable; PSA, probabilistic sensitivity analyses; RRR, relative risk reduction; SE, standard error.

Figure 2. Study schematic to estimate the value of trilaciclib for patients with ES-SCLC receiving first-line chemotherapy. Abbreviations. AE, adverse event; CEA, cost-effectiveness analysis; E/P/A, etoposide, carboplatin and atezolizumab; ES-SCLC, extensive-stage small cell lung cancer; QALY, quality-adjusted life year.

Table 3. Deterministic (base-case) results for first-line treatment of patients with ES-SCLC.

Parameter	Trilaciclib prior to E/P/A	E/P/A	Difference
Total number of AEs per patient	0.6	2.7	–2.1
Neutropenia	0.3	1.5	–1.3
Febrile neutropenia	0.02	0.1	–0.1
Anemia	0.3	0.5	–0.2
Thrombocytopenia	0.03	0.7	–0.6
Total costs per patient, $	99,919	118,759	–18,840
Treatment	83,545	49,537	34,008
E/P/A	49,537	49,537	0
Trilaciclib prior to E/P/A	34,008	0	34,008
Prophylactic use of G-CSF	2,541	5,082	–2,541
AE management	13,833	64,139	–50,307
Neutropenia	5,961	32,403	–26,442
Febrile neutropenia	429	1,715	–1,286
Anemia	6,649	11,755	–5,106
Thrombocytopenia	794	18,266	–17,472
QALYs per patient	0.150	0.145	0.005

All costs are presented in 2021 USD.

Abbreviations. AE, adverse event; E/P/A, etoposide, carboplatin, and atezolizumab; G-CSF, granulocyte colony-stimulating factor; QALY, quality-adjusted life year.

Figure 3. Incremental costs estimated from OWSAs. ^aUnderlying AE event rate and episode frequency were applied to both trilaciclib prior to E/P/A and E/P/A alone. ^bRRR of trilaciclib prior to E/P/A vs E/P/A alone. Abbreviations. AE, adverse event; E/P/A, etoposide, carboplatin, and atezolizumab; OWSA, one-way sensitivity analysis; RRR, relative risk reduction; USD, United States dollars.

Figure 4. Cost-effectiveness plane (A) and cost-effectiveness acceptability curve (B) for the PSA. Abbreviations. E/P/A, etoposide, carboplatin, and atezolizumab; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life year; USD, United States dollars; WTP, willingness-to-pay threshold.

Table 4. PSA results.

	Trilaciclib prior to E/P/A vs E/P/A
Incremental cost
Mean (SD)	−$18,999 ($8,596)
Median (95% CI)	−$18,268 (−$3,371, −$37,034)
Incremental QALYs
Mean (SD)	0.006 (0.030)
Median (95% CI)	0.007 (−0.052, 0.068)

Abbreviations. CI, confidence interval; E/P/A, etoposide, carboplatin, and atezolizumab; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life year; SD, standard deviation.

Daniel D, Kuchava V, Bondarenko I, et al. Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: a multicentre, randomised, double-blind, placebo-controlled phase II trial. Int J Cancer. 2021;148(10):2557–2570.

 PubMed Web of Science ®Google Scholar

Weiss JM, Csoszi T, Maglakelidze M, et al. Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019;30(10):1613–1621.

 PubMed Web of Science ®Google Scholar

Weiss J, Goldschmidt J, Andric Z, et al. Effects of trilaciclib on chemotherapy-induced myelosuppression and patient-reported outcomes in patients with extensive-stage small cell lung cancer: pooled results from three phase II randomized, double-blind, placebo-controlled studies. Clin Lung Cancer. 2021;22(5):449–460.

 PubMed Web of Science ®Google Scholar

Drugs.com [Internet]. Drug price information from Drugs.com; c2000-2021. 2019 [cited 2019 December 31]. Available from: https://www.drugs.com/price-guide/

 Google Scholar

Eldar-Lissai A, Cosler LE, Culakova E, et al. Economic analysis of prophylactic pegfilgrastim in adult cancer patients receiving chemotherapy. Value Health. 2008;11(2):172–179.

 PubMed Web of Science ®Google Scholar

Naeim A, Henk HJ, Becker L, et al. Pegfilgrastim prophylaxis is associated with a lower risk of hospitalization of cancer patients than filgrastim prophylaxis: a retrospective United States claims analysis of granulocyte colony-stimulating factors (G-CSF). BMC Cancer. 2013;13:11.

 PubMed Web of Science ®Google Scholar

Wong W, Yim YM, Kim A, et al. Assessment of costs associated with adverse events in patients with cancer. PLoS One. 2018;13(4):e0196007.

 PubMed Web of Science ®Google Scholar

Weycker D, Li X, Edelsberg J, et al. Risk and consequences of chemotherapy-induced febrile neutropenia in patients with metastatic solid tumors. J Oncol Pract. 2015;11(1):47–54.

 PubMed Web of Science ®Google Scholar

International Business Machines [Internet]. IBM Watson Health Micromedex® Red Book; 2021 [cited 2019 December 31]. Available from: https://www.ibm.com/uk-en/products/micromedex-red-book

 Google Scholar

Teckle P, McTaggart-Cowan H, Van der Hoek K, et al. Mapping the FACT-G cancer-specific quality of life instrument to the EQ-5D and SF-6D. Health Qual Life Outcomes. 2013;11:203.

 PubMed Web of Science ®Google Scholar

Data availability statement

The data that support the findings of this study are available from the co-author, H.H., upon reasonable request.