Carfilzomib and dexamethasone improves progression-free survival and response rates vs bortezomib and dexamethasone in patients (PTS) with relapsed multiple myeloma (RMM): The phase 3 study endeavor
Author(s): ,
Meletios Dimopoulos
Affiliations:
School of Medicine, National and Kapodistrian University of Athens,Athens,Greece
,
Philippe Moreau
Affiliations:
University of Nantes,Nantes,France
,
Antonio Palumbo
Affiliations:
University of Torino,Torino,Italy
,
Douglas Joshua
Affiliations:
Royal Prince Alfred Hospital,Camperdown,Australia
,
Ludek Pour
Affiliations:
University Hospital Brno,Brno,Czech Republic
,
Roman Hájek
Affiliations:
University Hospital Brno and Faculty of Medicine, University of Ostrava,Ostrava,Czech Republic
,
Thierry Facon
Affiliations:
CHRU Lille Hopital Claude Huriez,Lille,France
,
Heinz Ludwig
Affiliations:
Wilhelminen Cancer Research Institute, Wilhelminenspital,Vienna,Austria
,
Albert Oriol
Affiliations:
Institut Català d'Oncologia, Institut Josep Carreras, Hospital Germans Trias i Pujol,Barcelona,Spain
,
Hartmut Goldschmidt
Affiliations:
Heidelberg Medical University,Barcelona,Spain
,
Laura Rosiñol
Affiliations:
Hospital Clínic de Barcelona,Barcelona,Spain
,
Jan Straub
Affiliations:
Vseobecna fakultni nemocnice v Praze,Prague,Czech Republic
,
Aleksandr Suvorov
Affiliations:
First Republican Clinical Hospital of Udmurtia,Izhevsk,Russian Federation
,
Carla Araujo
Affiliations:
Centre Hospitalier de la Cote Basque,Bayonne,France
,
Elena Rimashevskaya
Affiliations:
Semashko Central Clinical Hospital,Moscow,Russian Federation
,
Tomas Pika
Affiliations:
University Hospital Olomouc,Olomouc,Czech Republic
,
Gianluca Gaidano
Affiliations:
Amedeo Avogadro University of Eastern Piedmont,Novara,Italy
,
Katja Weisel
Affiliations:
Universitatsklinikum Tubingen,Tubingen,Germany
,
Vesselina Goranova-Marinova
Affiliations:
University Multiprofile Hospital for Active Treatment Sveti Georgi,Plovdiv,Bulgaria
,
Anthony Schwarer
Affiliations:
Box Hill Hospital,Box Hill,Australia
,
Leonard Minuk
Affiliations:
London Health Sciences Centre, Western University, London,London,Guam
,
Tamás Masszi
Affiliations:
St. Istvan and St. Laszlo Hospital,Budapest,Hungary
,
Ievgenii Karamanesht
Affiliations:
Kyiv Center for Bone Marrow Transplantation,Kyiv,Ukraine
,
Massimo Offidani
Affiliations:
Clinica di Ematologia, Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi di Ancona,Ancona,Italy
,
Vania Hungria
Affiliations:
Irmandade da Santa Casa de Misericórdia de Sao Paulo,Sao Paulo,Brazil
,
Andrew Spencer
Affiliations:
Alfred Health-Monash University,Melbourne,Australia
,
Heidi Gillenwater
Affiliations:
Onyx Pharmaceuticals, Inc., an Amgen Subsidiary,South San Francisco,United States
,
Nehal Mohamed
Affiliations:
Onyx Pharmaceuticals, Inc., an Amgen Subsidiary,South San Francisco,United States
,
Shibao Feng
Affiliations:
Onyx Pharmaceuticals, Inc., an Amgen Subsidiary,South San Francisco,United States
Wee-Joo Chng
Affiliations:
National University Cancer Institute, National University Health System, Singapore and Cancer Science Institute of Singapore, National University of Singapore,Singapore,Singapore
EHA Learning Center. Dimopoulos M. Jun 14, 2015; 103385
Topic: 3Ec Plasma cell myeloma (Multiple myeloma)
Disclosure(s): Consultancy fees, honoraria and travel costs from Celgene, Janssen and Onyx. Consultancy fees from Novartis, research funding from Genesis and Janssen-Cilag.
Prof. Dr. Meletios A Dimopoulos
Prof. Dr. Meletios A Dimopoulos

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Abstract
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Abstract: LB2071

Type: Late breaking abstracts

Presentation during EHA20: From 14.06.2015 12:00 to 14.06.2015 12:15

Location: Room A7

Background
Bortezomib and dexamethasone (Vd) is a standard-of-care regimen for RMM. Carfilzomib (20/27 mg/m2; 2–10 min intravenous [IV] infusion) is approved in Argentina, Israel, Mexico, and the United States for relapsed and refractory multiple myeloma and significantly improved progression-free survival (PFS) when given with lenalidomide and dexamethasone for RMM in the phase 3 study ASPIRE (NCT01080391; Stewart et al, N Engl J Med, 2015). In study PX-171-007 (NCT00531284), carfilzomib (20/56 mg/m2; 30-minute infusion) and dexamethasone (Kd) had promising activity in pts with RMM (Papadopoulos et al, J Clin Oncol, 2015).

Aims
ENDEAVOR (NCT01568866) compares Kd with Vd in pts with RMM. Results from a prespecified interim analysis are presented.

Methods
Adults with RMM (1─3 prior treatments) were eligible. Pts were randomized 1:1 and stratified by prior K or V (yes vs no), prior lines of treatment (1 vs 2–3), International Staging System stage (1 vs 2–3), and intended route of V (IV vs subcutaneous [SC]). The Kd arm received K (30-min IV infusion) on days (D) 1, 2, 8, 9, 15, 16 (20 mg/m2 on D1, 2 [cycle 1]; 56 mg/m2 thereafter) and dexamethasone (20 mg) on D1, 2, 8, 9, 15, 16, 22, 23 of a 28-day cycle. The Vd arm received V (1.3 mg/m2; IV or SC) on D1, 4, 8, 11 and dexamethasone (20 mg) on D1, 2, 4, 5, 8, 9, 11, 12 of a 21-day cycle. Cycles were repeated until disease progression or unacceptable toxicity. The primary end point was PFS assessed by an independent review committee. Secondary end points include overall survival (OS), overall response rate (ORR), duration of response (DOR), rate of peripheral neuropathy (PN), and safety.

Results
In total, 929 pts (Kd: 464; Vd: 465) were randomized. In the Vd arm, 83.6% of pts received SC bortezomib. Median treatment exposure was 39.9 weeks (Kd) and 26.8 weeks (Vd). Kd led to a 47% decrease in the risk of progression or death (hazard ratio, 0.53; 95% confidence interval [CI], 0.44–0.65; P<.0001), with a median PFS of 18.7 months (95% CI, 15.6–not estimable) in the Kd arm vs 9.4 months (95% CI, 8.4–10.4) in the Vd arm. OS data were immature (deaths: Kd=75; Vd=88); pts continue to be followed. Best overall responses are presented in the table. The median DOR was 21.3 months (Kd) and 10.4 months (Vd). Treatment discontinuation due to an adverse event (AE) occurred in 14.0% (Kd) and 15.7% (Vd) of pts. An AE led to dose reductions of K or V in 22.5% and 48.0% of pts, respectively; 61.9% of dose reductions in the Vd arm were due to neuropathy-related AEs vs 6.6% in the Kd arm. Rates of grade ≥2 PN (grouped term) were 6.3% in the Kd arm vs 32.0% in the Vd arm (P<.0001). The most common hematologic AEs (preferred terms; all grades) in the Kd and Vd arms, respectively, included anemia (39.3% vs 27.0%) and thrombocytopenia (20.5% vs 17.1%); the most common nonhematologic AEs (preferred terms; all grades) included diarrhea (30.9% vs 38.4%), fatigue (29.4% vs 28.5%), and dyspnea (28.5% vs 13.2%).Grade ≥3 AEs of interest in the Kd and Vd arms, respectively, included hypertension (preferred term; 8.9% vs 2.6%), dyspnea (preferred term; 5.4% vs 2.2%), cardiac failure (grouped term; 4.8% vs 1.8%), and acute renal failure (grouped term; 4.1% vs 2.6%). A total of 3.9% of pts in the Kd arm and 3.4% of pts in the Vd arm died on study owing to AEs.

Summary
Carfilzomib and dexamethasone demonstrated statistically significant and clinically meaningful superiority over bortezomib and dexamethasone in RMM, with a 2-fold improvement in median PFS and a favorable benefit–risk profile. These data suggest that carfilzomib could be a best-in-class agent for RMM.

Keyword(s): Myeloma, Phase III, Proteasome inhibitor

Session topic: Myeloma and other monoclonal gammopathies - Clinical
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