Contributions
Abstract: S458
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 16:30 - 16:45
Location: Hall A
Background
In a phase 3 head-to-head comparison of two proteasome inhibitors (PIs) in patients with relapsed or refractory multiple myeloma (RRMM), ENDEAVOR, progression-free survival (PFS) was shown to be significantly longer with carfilzomib and dexamethasone (Kd) than with bortezomib and dexamethasone (Vd) (median 18.7 months vs 9.4 months, hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.44–0.65; P < 0.0001; Dimopoulos MA et al. Lancet Oncol. 2016;17:27–38).
Aims
Results from a planned second interim overall survival (OS) analysis of ENDEAVOR are presented here.
Methods
Patients who had RRMM and had received 1–3 prior lines of therapy were randomized in a 1:1 ratio to receive Kd or Vd. In the Kd arm, carfilzomib was given on days 1, 2, 8, 9, 15, and 16 (20 mg/m2 on days 1, 2 of cycle 1; 56 mg/m2 thereafter) and dexamethasone 20 mg was given on days 1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles. In the Vd arm, bortezomib (1.3 mg/m2) was given intravenously or subcutaneously on days 1, 4, 8, and 11 and dexamethasone 20 mg was given on days 1, 2, 4, 5, 8, 9, 11, and 12 of 21-day cycles. Patients were treated until progression or withdrawal of consent. OS was compared between treatment arms using a stratified log-rank test.
Results
The median treatment duration was 48 weeks for carfilzomib (N=464) and 27 weeks for bortezomib (N=465), with a median follow up of 38 months for Kd and 37 months for Vd. The median OS (95% CI) was 47.6 (42.5-NE) months in the Kd arm and 40.0 (32.6-42.3) months in the Vd arm, and all-cause mortality was significantly reduced with Kd vs Vd (HR, 0.791; 95% CI, 0.648-0.964; 1-sided p = 0.0100). The overall survival benefit was consistent regardless of prior bortezomib therapy (HR 0.75 for Kd vs Vd, no prior bortezomib; HR 0.84 for Kd vs Vd, prior bortezomib) and across all age groups (HR, 0.85 <65 yo; 0.71, 65-74 yo; 0.84, >75 yo), baseline ECOG performance status groups (HR, 0.81, ECOG 0; 0.80, ECOG 1; 0.50, ECOG 2), cytogenetic risk groups (HR, 0.83, high risk; 0.85, standard risk), and number of prior lines of therapy (HR, 0.83, 1 prior line; 0.76, 2-3 prior lines). The most frequent any-grade adverse events in the Kd arm were (Kd vs Vd) anemia (42.5% vs 28.3%), diarrhea (36.3% vs 40.6%), pyrexia (32.4% vs 15.4%), dyspnea (32.2% vs 13.6%), fatigue (32.2% vs 30.7%), and hypertension (32.2% vs 9.9%). Grade 3 or higher adverse events were experienced by 81.4% of patients in the Kd arm and 71.1% of patients in the Vd arm.
Conclusion
ENDEAVOR was the first randomized phase 3 trial to directly compare two different PIs in RRMM. Patients who received Kd had significantly longer OS compared with patients who received Vd. Safety results were comparable with those previously reported in the PFS interim analysis for ENDEAVOR.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Proteasome inhibitor, Multiple Myeloma, Clinical Trial
Abstract: S458
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 16:30 - 16:45
Location: Hall A
Background
In a phase 3 head-to-head comparison of two proteasome inhibitors (PIs) in patients with relapsed or refractory multiple myeloma (RRMM), ENDEAVOR, progression-free survival (PFS) was shown to be significantly longer with carfilzomib and dexamethasone (Kd) than with bortezomib and dexamethasone (Vd) (median 18.7 months vs 9.4 months, hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.44–0.65; P < 0.0001; Dimopoulos MA et al. Lancet Oncol. 2016;17:27–38).
Aims
Results from a planned second interim overall survival (OS) analysis of ENDEAVOR are presented here.
Methods
Patients who had RRMM and had received 1–3 prior lines of therapy were randomized in a 1:1 ratio to receive Kd or Vd. In the Kd arm, carfilzomib was given on days 1, 2, 8, 9, 15, and 16 (20 mg/m2 on days 1, 2 of cycle 1; 56 mg/m2 thereafter) and dexamethasone 20 mg was given on days 1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles. In the Vd arm, bortezomib (1.3 mg/m2) was given intravenously or subcutaneously on days 1, 4, 8, and 11 and dexamethasone 20 mg was given on days 1, 2, 4, 5, 8, 9, 11, and 12 of 21-day cycles. Patients were treated until progression or withdrawal of consent. OS was compared between treatment arms using a stratified log-rank test.
Results
The median treatment duration was 48 weeks for carfilzomib (N=464) and 27 weeks for bortezomib (N=465), with a median follow up of 38 months for Kd and 37 months for Vd. The median OS (95% CI) was 47.6 (42.5-NE) months in the Kd arm and 40.0 (32.6-42.3) months in the Vd arm, and all-cause mortality was significantly reduced with Kd vs Vd (HR, 0.791; 95% CI, 0.648-0.964; 1-sided p = 0.0100). The overall survival benefit was consistent regardless of prior bortezomib therapy (HR 0.75 for Kd vs Vd, no prior bortezomib; HR 0.84 for Kd vs Vd, prior bortezomib) and across all age groups (HR, 0.85 <65 yo; 0.71, 65-74 yo; 0.84, >75 yo), baseline ECOG performance status groups (HR, 0.81, ECOG 0; 0.80, ECOG 1; 0.50, ECOG 2), cytogenetic risk groups (HR, 0.83, high risk; 0.85, standard risk), and number of prior lines of therapy (HR, 0.83, 1 prior line; 0.76, 2-3 prior lines). The most frequent any-grade adverse events in the Kd arm were (Kd vs Vd) anemia (42.5% vs 28.3%), diarrhea (36.3% vs 40.6%), pyrexia (32.4% vs 15.4%), dyspnea (32.2% vs 13.6%), fatigue (32.2% vs 30.7%), and hypertension (32.2% vs 9.9%). Grade 3 or higher adverse events were experienced by 81.4% of patients in the Kd arm and 71.1% of patients in the Vd arm.
Conclusion
ENDEAVOR was the first randomized phase 3 trial to directly compare two different PIs in RRMM. Patients who received Kd had significantly longer OS compared with patients who received Vd. Safety results were comparable with those previously reported in the PFS interim analysis for ENDEAVOR.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Proteasome inhibitor, Multiple Myeloma, Clinical Trial