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

Dimopoulos, Meletios Α.; Moreau, Philippe; Palumbo, Antônio; Joshua, Douglas; Pour, Luděk; Hájek, Roman; Façon, Thierry; Ludwig, Heinz; Oriol, Albert; Goldschmidt, Hartmut; Rosiñol, Laura; Štraub, Jan; Suvorov, Aleksandr; Araujo, Carla; Rimashevskaya, Elena; Pika, Tomáš; Gaïdano, Gianluca; Weisel, Katja; Goranova-Marinova, Vesselina; Schwarer, Anthony P.; Minuk, Leonard; Masszi, Tamás; Karamanesht, Ievgenii; Offidani, Massimo; Hungria, Vânia; Spencer, Andrew; Orłowski, Robert Z.; Gillenwater, Heidi H.; Mohamed, Nehal; Feng, Shibao; Chng, Wee Joo

doi:10.1016/s1470-2045(15)00464-7

Cited by 772 publications

(859 citation statements)

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“…10,15 More recently, OS data showed superiority of Kd vs Vd and KRd vs Rd, with a nearly 8-month increase in median OS in patients treated with carfilzomib. 11,28 Carfilzomib-based regimens have been generally well tolerated, but concerns for CV toxicity have been raised.…”

Section: Discussionmentioning

confidence: 99%

“…11,28 Carfilzomib-based regimens have been generally well tolerated, but concerns for CV toxicity have been raised. 10,[13][14][15]29 Here, we assessed carfilzomib-associated CV AEs in phase 1-3 clinical trials. Across all RRMM phase 3 trials, treatment with carfilzomib was associated with a numeric increase in cardiac AE incidence.…”

Section: Discussionmentioning

confidence: 99%

“…9 In the head-to-head ENDEAVOR study comparing carfilzomib plus dexamethasone (Kd) with bortezomib plus dexamethasone (Vd), Kd improved the complete response rate, doubled progression-free survival (PFS), and reduced the risk for death by 21%. 10,11 Carfilzomib-based combinations have significantly improved PFS and overall survival (OS) by ;9 and 8 months, respectively, compared with standard treatments (lenalidomide plus dexamethasone [Rd] and Vd) in RRMM patients. Moreover, at first relapse, Kd and carfilzomib, lenalidomide, and dexamethasone (KRd) have improved PFS by 12 months compared with Rd and Vd.…”

Section: Introductionmentioning

confidence: 99%

“…12 In pivotal phase 2 and 3 studies, there has been a reported increase in CV AEs. 10,[13][14][15] In the phase 3 ASPIRE and ENDEAVOR studies, the grade $3 cardiac failure incidence was 3.8% (KRd) vs 1.8% (Rd) and 4.8% (Kd) vs 1.8% (Vd). 10,15 Post hoc analyses of ASPIRE and ENDEAVOR data according to age showed increased cardiac failure risk in elderly patients.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials

et al. 2018

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“…To this point, the randomized Phase III ENDEAVOUR trial conducted a head-to-head comparison of carfilzomib-dexamethasone versus bortezomib-dexamethasone in 929 patients with relapsed MM [16]. With a median follow-up of 11.5 months, the median PFS and ORR were 18.7 months and 77% in the carfilzomib group versus 9.4 months and 63% in the bortezomib group (p < 0.0001), respectively [16]. No difference in OS was detected at last reported follow-up.…”

Section: Carfilzomib (Kyprolis®)mentioning

confidence: 99%

The next generation of novel therapies for the management of relapsed multiple myeloma

Gonsalves

Milani

Derudas³

et al. 2016

Future Oncol.

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The advent of various novel therapies such as immunomodulators and proteasome inhibitors has transformed the treatment paradigm for patients with multiple myeloma (MM). As a result, the overall survival has improved dramatically over the last decade. Despite these advances, MM remains mostly incurable and most patients experience disease relapse after enjoying a period of disease control or remission. Fortunately, the scientific community continues to make strides in developing ‘next-generation’ therapies for the management of patients with relapsed MM. This review will summarize the efficacy of some of the newest therapeutic agents available for the treatment of patients with relapsed MM after their upfront treatment with the original novel agents such as thalidomide, lenalidomide and bortezomib.

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Diagnosis and Management of Multiple Myeloma

Cowan

Green

Kwok

et al. 2022

JAMA

511

272

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ultiple myeloma is a hematologic malignancy characterized by abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive osseous bone lesions, acute kidney injury, anemia, and hypercalcemia. The median age at onset of multiple myeloma is 69 years, and approximately 63% of patients diagnosed with multiple myeloma are older than 65 years. 1 In 2021, an estimated 34 290 new diagnoses of multiple myeloma and 12 410 deaths occurred in the US. In 2019, more than 155 688 people were diagnosed with multiple myeloma worldwide. 2 Approximately 100 000 deaths from multiple myeloma occur each year worldwide. 1 This review summarizes current evidence regarding the epidemiology, clinical presentation, diagnosis, and management of multiple myeloma. MethodsA literature search of the PubMed database was performed between January 1, 2000, through October 6, 2021, for Englishlanguage studies of the epidemiology, diagnosis, clinical presentation, and treatment of multiple myeloma. Additional papers were identified from review of the references from identified relevant articles. A total of 111 reports were identified and reviewed. IMPORTANCE Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Multiple myeloma is diagnosed in an estimated 34 920 people in the US and in approximately 588 161 people worldwide each year. OBSERVATIONS Among patients with multiple myeloma, approximately 73% have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation. Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging. The Revised International Staging System combines data from the serum biomarkers β 2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization-t(4;14), del(17p), and t(14;16)-to assess estimated progression-free survival and overall survival. At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82%. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. This induction therapy combined with autologous hematopoietic stem cell transplantation followed by...

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

Abstract: Onyx Pharmaceuticals, Inc., an Amgen subsidiary.

Cited by 772 publications

References 22 publications

Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials

Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials

The next generation of novel therapies for the management of relapsed multiple myeloma

Diagnosis and Management of Multiple Myeloma

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