Background
Methods
Predictive model for the management of mCRPC
Transition probabilities
Primary medication | AA | AAwd | Abiraterone before docetaxel | Abiraterone after docetaxel | Docetaxel | Cabazitaxel |
---|---|---|---|---|---|---|
Source
| [17] | [18] | [20] | [34] | [26] | [36] |
Median duration of PSA response (months)
| 12 (3–18) | 7.7 (95% CI: 7.1-8.6) | ||||
Median time to PSA progression (months)
| 5.9 (95% CI: 5.3-10.1) | 11.1 | 10.2 | 6.4 (IQR: 2.2-10.1) | ||
Mean time to PSA progression (months)
| ||||||
Progression free-survival (months)
| 16.5 | 5.6 | 2.8 (95% CI: 2.4-3.0) | |||
Rate of mortality
| 50% | 50% at 16.7 months | 42% | 50% at 18.9 months | 62% | |
at the end of the study | & | at the time of preplanned interim analysis | & | at the time of cut-off | ||
90% at 60 months | 82.8% at 3 years | |||||
Median survival time (months)
| 16.7 (95% CI: 14.3 - 21.5) | 14.8 (95% CI: 14.1-15.4) | 18.9 (95% CI: 17–21.2) | 15.1 (95% CI: 14.1-16.3) | ||
Median length of follow-up (months)
| 24 (range: 3–54) | 22.2 | 12.8 | 20.8 | 12.8 (IQR:, 7.8-16.9) | |
Median cycles of treatment
| 8 (range: 1–21) | 9.5* (range: 1–11) | 6* (IQR: 3–10) | |||
Median cycle of treatment (monthly equivalent)
| 7.13 (range: 1–8.3) | 5 (IQR: 2.3-7.5) |
Cost assignments
Cost analyses
Sensitivity analysis
Results
Probabilities and cost estimations
Medication | Dosage (reference) | Unit cost (reference) | Cost per month | ||
---|---|---|---|---|---|
Primary medication
| |||||
Bicalutamide (Casodex) | 1 × 50 mg daily | [17] | $1.61 per tablet (50 mg) | [42] | $58.71 |
Abiraterone (Zytiga) | 4 × 250 mg daily | [34] | $28.3333 per tablet (250 mg) | [42] | $3,448 |
Cabazitaxel (Jevtana) | 25 mg/m2 i.v. every 21 days | [36] | $5,840 per vial (60 mg/1.5 ml) | [46] | $8,460*
|
Docetaxel (Taxotere) | 75 mg/m2 i.v. every 21 days | [26] | $599.79 per vial (160 mg/16 ml)**
| [46] | $774*
|
Prednisone (Deltasone) | 2 × 5 mg daily | [34] | $0.022 per tablet (5 mg)**
| [42] | $1.34 |
Premedication for chemotherapy-induced side effects
| |||||
Dexamethasone†‡
| 8 mg i.v. every 21 days | $3.24 per vial (10 mg/ml, 1 ml)**
| [46] | $4.69 | |
Diphenhydramine†
| 25 mg i.v. every 21 days | [36] | $2.98 per vial (50 mg/ml, 1 ml)**
| [46] | $4.32 |
Famotidine†
| 20 mg i.v. every 21 days | [36] | $2.71 per vial (10 mg/ml, 2 ml)**
| [46] | $3.93 |
Medication for medical castration
| |||||
Goserelin (Zoladex) | 10.8 mg s.c. every 3 months (13 weeks) | [40] | $1,113 per 10.8 mg depot 3 months | [42] | $371 |
Bone-targeted therapy
| |||||
Denosumab (XGEVA) | 120 mg s.c. every 4 weeks | [23] | $538.45 per vial (120 mg/1.7 ml) | [42] | $585 |
Simulated treatment sequence, duration of treatments, survival in mCRPC and validity of the predictive models
Current model
| ||||||
---|---|---|---|---|---|---|
Treatment sequence | AA | AAwd | Docetaxel | Abiraterone | OtherTx | |
% of patients receiving each line of treatment | 100% | 88.1% | 72.7% | 54.2% | 29.4% | |
Mean duration per patient (95%CI)*
| 8.5 (8.4-8.6) | 4.3 (4.3-4.4) | 7.1 (7.0-7.1) | 10 (9.9-10.2) | 14.6 (14.3-14.9) | |
Median duration per patient (IQR)*
| 8 (5–12) | 4 (3–6) | 7 (7–8) | 9 (4–17) | 15 (6–24) | |
Mean Survival (95%CI)**
| 28.1 (27.7-28.4) | 22.1 (21.7-22.4) | 21.3 (20.9-21.6) | 18.8 (18.4-19.1) | 15.2 (14.9-15.5) | |
Median Survival (IQR)**
| 25 (14–40) | 19 (7–24) | 18 (9–32) | 16 (8–28) | 16 (7–24) | |
Alternate model
| ||||||
Treatment sequence
|
AA
|
AAwd
|
Abiraterone
|
Docetaxel
|
Cabazitaxel
|
OtherTx
|
% of patients receiving each line of treatment | 100% | 88.0% | 72.6% | 47.4% | 35.4% | 26.9% |
Mean duration per patient (95%CI)*
| 8.6 (8.5-8.7) | 4.4 (4.3-4.4) | 20.2 (19.9- 20.4) | 7.0 (7.0-7.1) | 5.7 (5.6-5.8) | 15.0 (14.7-15.4) |
Median duration per patient (IQR)*
| 8 (5–12) | 4 (3–6) | 19 (9–35) | 7 (7–8) | 5 (4–7) | 16 (7–24) |
Mean Survival (95%CI)**
| 37.3 (36.8-37.8) | 32.5 (32.0-32.9) | 33.8 (33.4.0-34.3) | 20.4 (20.1-20.8) | 17.6 (17.3-17.9) | 15.7 (15.4-16.0) |
Median Survival (IQR)**
| 34 (15–56) | 30.0 (12–50) | 32 (17–48) | 18 (9–34) | 17 (8–28) | 17 (8–24) |
Estimated cost of mCRPC medications by line of treatment
Treatment sequence | Primary medication | Medication for medical castration*
| Bone-targeted therapy**
| Total | ||||
---|---|---|---|---|---|---|---|---|
Current model
| Mean cost (95%CI) | Median cost (IQR) | Mean cost (95%CI) | Median cost (IQR) | Mean cost (95%CI) | Median cost (IQR) | Mean cost (95%CI) | Median cost (IQR) |
AA | $500 | $410 | $3,002 | $2,467 | $4,485 | $3,686 | $7,988 | $6,563 |
($495-$505) | ($293-$705) | ($2,972-$3,032) | ($1,762-$4,229) | ($4,440-$4,530) | ($2,633-$6,318) | ($7,907-$8,067) | ($4,688-$11,251) | |
AAwd | $0 | $0 | $1,526 | $1,409 | $2,280 | $2,106 | $3,806 | $3,515 |
($1,513-$1,538) | ($1,057-$2,114) | ($2,261-$2,299) | ($1,580-$3,159) | ($3,775-$3,837) | ($2,636-$5,273) | |||
Docetaxel | $6,172 | $6,124 | $2,487 | $2,467 | $3,715 | $3,686 | $12,374 | $12,277 |
($6,126-$6,219) | ($6,124-$6,999) | ($2,467-$2,506) | ($2,467-$2,819) | ($3,687-$3,743) | ($3,686-$4,212) | ($12,280-$13,468) | ($12,277-$14,031) | |
Abiraterone | $34,624 | $31,040 | $3,538 | $3,172 | $5,285 | $4,739 | $43,448 | $38,950 |
($34,032-$35,217) | ($13,796-$58,631) | ($3,477-$3,599) | ($1,409-$5,991) | ($5,195-$5,376) | ($2,106-$8,950) | ($42,706-$44,192) | ($17,311-$73,573) | |
OtherTx | $0 | $0 | $5,130 | $5,287 | $7,664 | $7,898 | $12,794 | $13,184 |
($5,021-$5,239) | ($2,115-$8,459) | ($7,501-$7,862) | ($3,159-$12,636) | ($12,523-$13,065) | ($5,274-$21,095) | |||
Alternate model
| ||||||||
AA | $504 | $470 | $3,025 | $2,819 | $4,519 | $4,212 | $8,049 | $7,501 |
($498-$509) | ($294-$704) | ($2,995-$3,055) | ($1,762-$4,229) | ($4,474-$4,564) | ($2,632-$6,318) | ($7,968-$8,128) | ($4,688-$11,251) | |
AAwd | $0 | $0 | $1,541 | $1,410 | $2,303 | $2,106 | $3,844 | $3,515 |
($1,529-$1,554) | ($1,057-$2,115) | ($2,283-$2,321) | ($1,580-$3,159) | ($3,812-$3,874) | ($2,637-$5,273) | |||
Abiraterone | $69,512 | $65,531 | $7,103 | $6,697 | $10,611 | $10,003 | $87,227 | $82,231 |
($68,593-$70,431) | ($31,041-$120,715) | ($7,009-$7,197) | ($3,172-$12,335) | ($10,470-$10,751) | ($4,738-$18,428) | ($86,073-$88,381) | ($38,952-$151,478) | |
Docetaxel | $6,143 | $6,118 | $2,477 | $2,467 | $3,701 | $3,686 | $12,321 | $12,271 |
($6,083-$6,203) | ($6,118-$6,992) | ($2,453-$2,501) | ($2,467-$2,819) | ($3,665-$3,737) | ($3,686-$4,212) | ($12,201-$12,441) | ($12,271-$14,024) | |
Cabazitaxel | $49,131 | $43,125 | $2,007 | $1,762 | $2,999 | $2,632 | $54,138 | $47,519 |
($48,366-$49,895) | ($34,500-$60,375) | ($1,977-$2,038) | ($1,409-$2,467) | ($2,952-$3,046) | ($2,106-$3,685) | ($53,295-$54,980) | ($38,016-$66,528) | |
OtherTx | $0 | $0 | $5,300 | $5,639 | $7,918 | $8,424 | $13,217 | $14,063 |
($5,186-$5,414) | ($2,467-$8,459) | ($7,747-$8,087) | ($3,685-12,636) | ($12,933-$13,501) | ($6,153-$21,095) |
Total cost of medications over the mCRPC period
Total mCRPC cost per patient | Monthly mCRPC cost per patient | Total mCRPC cost in Canada | |||
---|---|---|---|---|---|
Current model
| Mean (95%CI) | Median (IQR) | Mean (95%CI) | (annual cohort of 4,000 mCRPC patients) | |
Medication type:
| |||||
Primary medication*
| $23,745 ($23,238-$24,253) | $13,316 ($939-$41,553) | $845 ($827-$882) | $94,980,000 | 49.1% |
Medication for medical castration†
| $9,898 ($9,779-$10,016) | $8,811 ($4,934-$14,098) | $352 ($348-$357) | $39,592,000 | 20.4% |
Bone-targeted therapy‡
| $14,785 ($14,607-$14,963) | $13,163 ($7,371-$21,060) | $526 ($520-$532) | $59,032,000 | 30.5% |
Total cost of mCRPC
| $48,428 ($47,624-$49,232) | $35,290 ($13,244-$76,711) | $1,723 ($1,695-$1,752) | $193,604,000 | 100.0% |
Alternate model
| |||||
Medication type:
| |||||
Primary medication**
| $71,302 ($70,026-$72,579) | $62,816 ($939-$123,501) | $1,912 ($1,877-$1,946) | $285,208,000 | 68.5% |
Medication for medical castration†
| $13,140 ($12,971-$13,309) | $11,983 ($5,639-$19,737) | $352 ($348-$357) | $52,560,000 | 12.6% |
Bone-targeted therapy‡
| $19,629 ($19,376-$19,882) | $17,901 ($8,424-$29,484) | $526 ($520-$532) | $78,516,000 | 18.9% |
Total cost of mCRPC
| $104,071 ($102,373-$105,770) | $92,700 ($15,002-$172,722) | $2,790 ($2,745-$2,835) | $416,284,000 | 100.0% |
Sensitivity analysis
mCRPC cost (per patient) | Monthly mCRPC cost | ||
---|---|---|---|
Mean (95%CI) | Median (IQR) | Mean (95%CI) | |
Scenario 1: Variation of the probability of transition from docetaxel to subsequent treatment
| |||
Current model
| |||
10% increase of transition to abiraterone
| $48,049 ($47,451-$48,778) | $39,395 ($14,465-$77,508) | $1,743 ($1,721-$1,769) |
20% increase of transition to abiraterone
| $48,096 ($47,467-$48,817) | $39,669 ($13,888-$76,884) | $1,766 ($1,743-$1,793) |
10% decrease of transition to abiraterone
| $48,026 ($47,253-$48,697) | $36,064 ($14,006-$75,805) | $1,707 ($1,680-$1,731) |
20% decrease of transition to abiraterone
| $48,049 ($47,125-$48,783) | $36,402 ($14,407-$76,710) | $1,706 ($1,673-$1,732) |
Alternate model
| |||
10% increase of transition to cabazitaxel
| $102,998 ($101,424-$104,765) | $92,113 ($16,165-$170,454) | $2,814 ($2,771-$2,862) |
20% increase of transition to cabazitaxel
| $102,846 ($101,065-$104,960) | $90,435 ($16,760-$171,956) | $2,833 ($2,784-$2,891) |
10% decrease of transition to cabazitaxel
| $103,626 ($102,001-$105,506) | $94,951 ($16,466-$171,206) | $2,801 ($2,757-$2,852) |
20% decrease of transition to cabazitaxel
| $103,784 ($102,169-$105,513) | $95,900 ($16,165-$173,512) | $2,802 ($2,758-$2,849) |
Scenario 2: 20%
, 30%
and 50%
of patients received docetaxel retreatment after docetaxel
| |||
Current model
| |||
20% of patients received docetaxel retreatment
| $45,312 ($44,693-$45,873) | $34,732 ($14,469-$71,373) | $1,615 ($1,593-$1,635) |
30% of patients received docetaxel retreatment
| $43,925 ($43,302-$44,522) | $34,592 ($13,888-$68,665) | $1,565 ($1,543-$1,587) |
50% of patients received docetaxel retreatment
| $41,182 ($40,607-$41,964) | $32,188 ($13,649-$62,930) | $1,467 ($1,447-$1,495) |
Alternate model
| |||
20% of patients received docetaxel retreatment
| $99,887 ($98,628-$101,220) | $90,204 ($15,764-$168,696) | $2,705 ($2,671-$2,741) |
30% of patients received docetaxel retreatment
| $98,335 ($96,877-$99,735) | $88,783 ($16,643-$164,680) | $2,660 ($2,620-$2,698) |
50% of patients received docetaxel retreatment
| $95,227 ($93,735-$96,347) | $88,644 ($16,584-$163,683) | $2,577 ($2,537-$2,607) |
Scenario 3: 50%
, 70%
and 100%
received AA before mCRPC phase
| |||
Current model
*
| |||
50% of patients received AA before entering mCRPC phase
| $48,378 ($47,841-$49,042) | $39,452 ($13,829-$76,165) | $2,160 ($2,136-$2,189) |
70% of patients received AA before entering mCRPC phase
| $48,459 ($47,750-$49,169) | $39,452 ($14,006-$77,391) | $2,233 ($2,200-$2,266) |
100% of patients received AA before entering mCRPC phase
| $48,532 ($47,780-$49,329) | $40,876 ($13,155-$75,612) | $2,357 ($2,321-$2,396) |
Alternate model
**
| |||
50% of patients received AA before entering mCRPC phase
| $113,645 ($112,019-$115,416) | $109,405 ($37,800-$175,884) | $3,433 ($3,384-$3,487) |
70% of patients received AA before entering mCRPC phase
| $117,895 ($116,248-$119,549) | $112,648 ($44,486-$174,101) | $3,562 ($3,512-$3,612) |
100% of patients received AA before entering mCRPC phase
| $124,300 ($123,133-$125,472) | $122,061 ($59,878-$177,657) | $3,758 ($3,722-$3,793) |
Scenario 4: Variation of the rate of patients transiting to docetaxel (Current model)/abiraterone (Alternate model)
†
| |||
Current model
| |||
90% of patients transit to docetaxel
| $51,936 ($51,147-$52,584) | $44,070 ($17,843-$80,975) | $1,893 ($1,865-$1,917) |
80% of patients transit to docetaxel
| $51,571 ($50,769-$52,390) | $43,459 ($16,760-$80,710) | $1,873 ($1,844-$1,903) |
70% of patients transit to docetaxel
| $51,106 ($50,399-$51,797) | $42,377 ($16,333-$79,588) | $1,851 ($1,825-$1,876) |
Alternate model
| |||
90% of patients transit to abiraterone
| $117,515 ($115,852-$118,932) | $115,641 ($45,674-$177,184) | $3,086 ($3,042-$3,123) |
80% of patients transit to abiraterone
| $115,974 ($114,204-$117,959) | $113,188 ($42,052-$176,342) | $3,054 ($3,008-$3,107) |
70% of patients transit to abiraterone
| $114,245 ($112,716-$115,980) | $111,760 ($37,922-$176,258) | $3,022 ($2,981-$3,067) |