Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study

Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). Interpretation: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. Funding: Onyx Pharmaceuticals, Inc., an Amgen subsidiary

Malignant Lymphatic and Hematopoietic Neoplasms Mortality in Serbia, 1991–2010: A Joinpoint Regression Analysis

BACKGROUND: Limited data on mortality from malignant lymphatic and hematopoietic neoplasms have been published for Serbia. METHODS: The study covered population of Serbia during the 1991-2010 period. Mortality trends were assessed using the joinpoint regression analysis. RESULTS: Trend for overall death rates from malignant lymphoid and haematopoietic neoplasms significantly decreased: by -2.16% per year from 1991 through 1998, and then significantly increased by +2.20% per year for the 1998-2010 period. The growth during the entire period was on average +0.8% per year (95% CI 0.3 to 1.3). Mortality was higher among males than among females in all age groups. According to the comparability test, mortality trends from malignant lymphoid and haematopoietic neoplasms in men and women were parallel (final selected model failed to reject parallelism, P = 0.232). Among younger Serbian population (0-44 years old) in both sexes: trends significantly declined in males for the entire period, while in females 15-44 years of age mortality rates significantly declined only from 2003 onwards. Mortality trend significantly increased in elderly in both genders (by +1.7% in males and +1.5% in females in the 60-69 age group, and +3.8% in males and +3.6% in females in the 70+ age group). According to the comparability test, mortality trend for Hodgkin's lymphoma differed significantly from mortality trends for all other types of malignant lymphoid and haematopoietic neoplasms (P<0.05). CONCLUSION: Unfavourable mortality trend in Serbia requires targeted intervention for risk factors control, early diagnosis and modern therapy