This document discusses whether the standard of care for multiple myeloma should be changed from bortezomib to carfilzomib/dexamethasone. It notes that the only phase III data available comes from the ENDEAVOR trial, which showed carfilzomib doubled progression-free survival compared to bortezomib. However, bortezomib has proven effective in high-risk myeloma and salvage settings. Carfilzomib administration is more difficult due to its IV route and hydration requirements. Bortezomib has a more favorable tolerability profile and lower cost. The document concludes the standard of care should not be changed yet, as bortezomib

1. Should we change the standard of care to Carfilzomib/dexamethasone?
In favor of Bortezomib
Panisinee Lawasut, MD, MSc
Div. of Hematology
Dept. of Medicine
Chulalongkorn University

2. Efficacy Tolerability

3. ENDEAVOR

4. Efficacy: only phase III data available from ENDEAVOR
OS
n/a
PFS
Kd double PFS compare to Vd in RMM (18.7 vs 9.4 mo)
Duration of treatment, Treatment free survival, etc
n/a (Kd vs Vd Rx exposure: 39.9 vs 26.8 wk)
Dimopoulos M et al. J Clin Oncol 33, 2015 (suppl; abstr 8509)

5. Efficacy:
High risk myeloma
n/a
Carfilzomib:
Small N of pt from Phase II PX-171-003-A1 – not different
Main benefit were in those with t(4;14)
Bortezomib:
VD, PAD + MT, VTD improve outcomes in t(4;14)
Stem cell collection
Both have no impact on stem cell collection
Retreatment/ Salvage
Carfilzomib: n/a
Bortezomib: Yes, without impairing long term OS
Jakubowiak AJ et al. Leukemia. 2013;27(12):2351-6.
Lonial S et al. Blood. 2015 Aug 13.

6. Tolerability: only phase III data available from ENDEAVOR
Dimopoulos M et al. J Clin Oncol 33, 2015 (suppl; abstr 8509)
Kd (%) Vd (%)
Rx discontinuation due to AE 14.0 15.7
Death due to AE 3.9 3.4
Grade ≥ 3
- Hypertension
- Dysnea
- Cardiac failure
- Acute renal failure
8.9
5.6
4.8
4.1
2.6
2.3
1.8
2.6
PN grade ≥ 2 6.3 32.0*
Carfizomib: Renal impairment
High blood pressure
Posterior reversible encephalopathy syndrome (PRES)
Heart failure and increased cardiac events eg MI
Long term complication?

7. Tolerability: Carfilzomib administration is more difficult
Carfilzomib Bortezomib
2-consecutive days
IV route
IV hydration
Require more infusion hr
IV access problem in long term
Twice or once weekly
SC route feasible
IV hydration is option
Short daycare visit duration

8. Roy A et al. Am Health Drug Benefits. 2015;8(4):204-215
Tolerability: price

9. Should we change the standard of care to Carfilzomib/dexamethasone?
Not now
Bortezomib is still on its throne
Bortezomib is an effective old friend
with manageable toxicity and acceptable cost
Only selected population deserved a new treatment
until it proves its superiority either in survival or QoL
Q & A