Budget impact analysis of everolimus for the treatment of hormone receptor positive, human epidermal growth factor receptor-2 negative (HER2−) advanced breast cancer in Kazakhstan

Figures & data

Table 1. Market share with and without everolimus.

	1st line	2nd line	3rd line
Current market share (2015–2018)
Everolimus + letrozole	0%	0%	0%
Letrozole/anastrozole	15%	30%	30%
Chemotherapy	70%	70%	70%
Tamoxifen	15%	0%	0%
Total	100%	100%	100%
Market share with everolimus (2014)
Everolimus + letrozole	1.0%	1.0%	0.0%
Letrozole/anastrozole	15.0%	30.0%	30.0%
Chemotherapy	69.1%	69.0%	70.0%
Tamoxifen	14.9%	0.0%	0.0%
Total	100%	100%	100%
Market share with everolimus (2015)
Everolimus + letrozole	2.0%	2.0%	0.0%
Letrozole/anastrozole	15.0%	30.0%	30.0%
Chemotherapy	68.3%	68.0%	70.0%
Tamoxifen	14.7%	0.0%	0.0%
Total	100%	100%	100%
Market share with everolimus (2015–2018)
Everolimus + letrozole	3.0%	3.0%	0.0%
Letrozole/anastrozole	15.0%	30.0%	30.0%
Chemotherapy	67.5%	67.0%	70.0%
Tamoxifen	14.6%	0.0%	0.0%
Total	100%	100%	100%

Figure 1. Cumulative cohort approach.

Table 2. PFS and OS parameters.

	Everolimus + letrozole/ anastrozole	Letrozole/anastrozole	Chemotherapy	Tamoxifen
Weibull PFS σ parameter	0.067	0.191	0.064	0.133
Weibull PFS λ parameter	1.118	1.006	1.348	1
Weibull OS σ parameter	0.013	0.014	0.047	0.009
Weibull OS λ parameter	1.105	1.172	1.11	1.304
Mean estimated PFS	0.90	0.44	0.59	0.63
Mean estimated OS	2.98	2.49	0.68	2.17

Figure 2. Progression-free survival curves.

Figure 3. Overall survival curves.

Table 3. Drug costs.

	Dose (mg)	Unit size (mg per unit)	Pack size (no. units)	Cost per pack	Cost per unit	Cost per month
Letrozole	2.5	2.5	30	Т 9,309	Т 310	T 9,445
Anastrozole	1.0	1.0	28	Т 2,936	Т 105	T 3,191
Letrozole/Anastrozole*						T 6,318
Everolimus	10.0	10	30	Т 1,052,880	Т 35,096	T 1,068,235
Eve + Letrozole/Anastrozole						T 1,074,553
Tamoxifen	20.0	20	30	Т 690	Т 23	T 700

*The cost for letrozole/anastrozole is calculated as the mean cost of letrozole and anastrozole individually.

Source for cost of everolimus: {Order of Chairman of the Board of ‘SK-Pharmaceuticals’ LLP № 06/62 as of June 10, 2013}, Minister of Healthcare of the Republic of Kazakhstan Order No. 224 as of April, 15, 201317.

Source for costs of other drugs: based on average costs of drugs from http://pharmprice.kz/ database for the period June–September 2013 and the following official documents: Attachment to ‘Minister of Healthcare of the Republic of Kazakhstan Order No. 444 as of July, 1, 2011’18.

Table 4. Cost of chemotherapy regimes.

Chemotherapy regimens	Proportion of patients	Dose (mg)	Unit size (mg)	Pack size (no. units)	Cost per pack	Cost per unit	Units required per dose	Cost per dose	Doses per month	Cost per month
Docetaxel	60%	135	80	1.7	Т 151,298	Т 88,999	2	Т 177,998	1.45	Т 259,147
Doxorubicin	60%	108	50	2.2	Т 1,304	Т 593	3	Т 1,778	1.45	Т 3,734
Capecitabine	20%	63,000	500	112	Т 84,876	Т 758	126	Т 95,486	1.45	Т 139,554
Carboplatin	20%	600	150	4	Т 3,729	Т 932	4	Т 3,729	1.45	Т 6,561
Cyclophosphamide	60%	1,080	200	5.4	Т 97	Т 18	5	Т 97	1.45	Т 1,297
PEG-doxorubicin	3%	90	20	4.5	Т 77,798	Т 17,288	5	Т 77,798	1.45	Т 113,917
Epirubicin	20%	108	59	2.2	Т 1,870	Т 850	2	Т 1,700	1.45	Т 3,621
Fluorouracil	10%	1,080	250	4.3	Т 115	Т 27	5	Т 134	1.45	Т 1,351
Gemcitabine	5%	3,600	1000	3.6	Т 5,500	Т 1,528	4	Т 6,111	1.45	Т 10,014
Paclitaxel	30%	315	100	3.2	Т 12,100	Т 3,781	4	Т 15,125	1.45	Т 23,079
Vinorelbine	20%	90	10	9	Т 12,870	Т 1,430	9	Т 12,870	1.45	Т 19,810
Weighted* mean cost of all therapies (including T 2458 administration cost)										T 205,851

*The weighted mean cost is calculated using the proportion of patients receiving each drug.

Cost source: based on average costs of drugs from http://pharmprice.kz/ database for the period June–September 2013.

Table 5. Cost of adverse events.

	Eve + Letrozole/ Anastrozole	Letrozole/ Anastrozole	Chemotherapy	Tamoxifen	Costs	Assumptions
Stomatitis	8%	1%	9%	0%	Т 995	Micanazole + Mitronidazole
Rash	1%	0%	2%	0%	Т 1,000	Anhistamine (suprasin)
Fatigue	5%	1%	12%	6%	Т 2,000	Solamedrol
Diarrhoea	3%	1%	10%	0%	Т 1,444	Linex, Loperamide
Anorexia	1%	1%	0%	2%	Т 2,000	Solamedrol
Nausea	1%	1%	6%	0%	Т 1,950	Ondacentron + Cirucal
Cough	1%	0%	0%	0%	Т 280	Amburaxaan
Pneumonitis	0%	0%	0%	2%	Т 9,220	Cephalosporin + Amburaxan
Thromboembolic	0%	0%	0%	4%	Т 54,847	Klexan −30 days, Veraphalin
Pain	0%	0%	0%	10%	Т 15,300	Tramadol
Conjunctivitis	–	–	0%	–	Т 765	Eye drops
Infection	–	–	26%	–	Т 6,067	Cephalasporin + flucanozole
Fluid retention	–	–	3%	–	Т 6,350	Mannitol + Diacard
Peripheral neuropathy	–	–	5%	–	Т 10,320	Vitamines + TAD
Nail toxicity	–	–	5%	–	Т 467	Miconazole
Local phlebitis	–	–	1%	–	Т 980	Troxevasine or Heparin
Allergy	–	–	2%	–	Т 1,000	Anhistamine (suprasin)
Leukopenia	–	–	77%	–	Т 54,010	Filgrastim
Thrombocytopenia	–	–	3%	–	Т 256,200	Revolate
Anaemia	–	–	2%	–	Т 362,754	Epoetin
Weighted cost	Т257	Т72	Т59,477	Т4,068	–	–

Cost source: based on average costs of drugs from http://pharmprice.kz/ database for the period June–September 2013.

Table 6. Progression-free health state costs.

		All interventions excluding chemotherapy		Chemotherapy
	Unit cost	Resource use per month	Cost per month	Resource use per month	Cost per month
Costs of outpatient services
Clinical Oncologist	Т 768	1.00	Т 768	1.33	Т 1,021
GP visit	Т 640	–	–	1.33	Т 851
Clinical nurse specialist	Т 548	1.00	Т 548	2.00	Т 1,096
Ambulance	Т 2,188	–	–	1.00	Т 2,188
Psychotherapist	Т 768	–	–	1.00	Т 768
Outpatient care	Т 548	–	–	4.00	Т 2,192
Clinical nurse home visit	Т 548	–	–	4.00	Т 2,192
Total cost of palliative outpatient care per month			T 1316		Т 5,155
Costs of in-patient services
Clinical Oncologist	Т 768	–	–	1.33	Т 1,021
GP practices	Т 973	–	–	1.33	Т 1,294
Radiotherapy (40% of patients)	Т 774	–	–	20.00	Т 6,190
Hospitalization days (40% of patients)	Т 5,000	–	–	28.00	Т 56,000
Total cost of palliative in-patient care per month			T 0		Т 64,505
Laboratory tests
Complete blood count	Т 1,272	1.00	Т 1272	4.00	T 5,088
Blood chemistry panel	Т 2,795	1.00	Т 2795	4.00	T 11,180
Liver function test	Т 500	1.00	Т 500	4.00	T 2,000
ECG	Т 501	1.00	Т 501	1.00	T 501
Creatinine (urine)	Т 415	1.00	Т 415	4.00	T 1,661
Haematuria (urine)	Т 555	1.00	Т 555	4.00	T 2,220
Total laboratory costs			T 6038		Т 22,650
Additional methods of examination
CT scan	Т 7,820	–	–	0.30	T 2,346
Ultrasound (general & for breast)	Т 1,940	–	–	0.30	T 582
Conventional x-ray (breast 2 projections)	Т 891	–	–	0.30	T 267
Additional therapy
Antibiotics (Cephalosporin)	Т 9,220	–	–	10%	T 922
Analgesics (Tramadol)	Т 15,300	–	–	70%	T 10,710
Dexamethasone	Т 1,200	–	–	50%	T 600
Diphosphonate (Zometa)	Т 11,000	–	–	60%	T 6,600
Grand total cost per month for health state			T 7354		T 114,338

Cost source: based on average costs of drugs from http://pharmprice.kz/ database for the period June–September 2013.

Table 7. Post-progression treatment sequences.

Post-progression sequences	% patients receiving sequences	Average total time (months)	Average total cost per treatment sequence
Third line hormonal therapy + supportive palliative care	7%	7.8	Т 897,296.25
Chemotherapy + supportive palliative care	30%	15.8	Т 6,068,305.60
Third line hormonal therapy + chemotherapy  + supportive palliative care	51%	18.6	Т 7,156,722.69
Supportive palliative care	12%	5	Т 114,338
Total (weighted averages)	100%	15.4	Т 5,546,952
Average monthly cost			Т 360,848

Table 8. Budget impact analysis results.

	2014	2015	2016	2017	2018	Total costs
Without everolimus
Drug costs	703,479,209	195,477,482	147,656,460	157,025,334	170,388,963	1,374,027,447
Pre-prog costs	400,093,960	111,220,480	84,030,545	89,331,806	96,927,330	781,604,120
Post-prog costs	977,149,347	1,411,775,407	1,115,840,850	918,853,301	840,971,947	5,264,590,854
AE costs	32,392,258	5,559,744	6,036,552	6,554,252	7,116,350	57,659,156
Total	2,113,114,773	1,724,033,113	1,353,564,407	1,171,764,693	1,115,404,590	7,477,881,577
With everolimus
Drug costs	741,488,831	221,657,242	177,187,186	189,717,645	206,101,774	1,536,152,678
Pre-prog costs	396,516,235	109,687,140	81,949,741	87,015,993	94,411,068	769,580,177
Post-prog costs	979,190,462	1,418,446,421	1,127,149,398	933,523,890	858,542,150	5,316,852,320
AE costs	32,073,459	5,451,431	5,860,150	6,362,721	6,908,393	56,656,154
Total	2,149,268,987	1,755,242,234	1,392,146,475	1,216,620,248	1,165,963,385	7,679,241,328
Incremental impact of introducing everolimus
Drug costs	38,009,622	26,179,760	29,530,726	32,692,311	35,712,812	162,125,231
Pre-prog costs	−3,577,725	−1,533,340	−2,080,804	−2,315,813	−2,516,262	−12,023,944
Post-prog costs	2,041,115	6,671,013	11,308,548	14,670,588	17,570,202	52,261,466
AE costs	−318,799	−108,313	−176,403	−191,531	−207,957	−1,003,002
Total	36,154,213	31,209,120	38,582,067	44,855,556	50,558,795	201,359,752

Figure 4. Sensitivity analyses.

Order of Chairman of the Board of ‘SK-Pharmaceuticals’ LLP No. 06/62 as of June 10, 2013

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Minister of Health. Attachment 1, 2 to Minister of Healthcare of the Republic of Kazakhstan Order No. 444 as of July 1, 2011. Kazakhstan: Ministry of Health, 2013

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