Abstract:

The randomized phase 3 ENDEAVOR study (N=929) compared carfilzomib and dexamethasone (Kd) with bortezomib and dexamethasone (Vd) in relapsed multiple myeloma (RMM). We performed a subgroup analysis from ENDEAVOR in patients categorized by number of prior lines of therapy or by prior treatment. Median progression-free survival (PFS) for patients with one prior line was 22.2 months for Kd vs 10.1 months for Vd, and median PFS for patients with ≥2 prior lines was 14.9 months for Kd vs 8.4 months for Vd. For patients with prior bortezomib exposure, the median PFS was 15.6 months for Kd vs 8.1 months for Vd, and for patients with prior lenalidomide exposure the median PFS was 12.9 months for Kd vs 7.3 months for Vd. Overall response rates (Kd vs Vd) were 81.9 vs 65.5% (one prior line), 72.0 vs 59.7% (≥2 prior lines), 71.2 vs 60.3% (prior bortezomib) and 70.1 vs 59.3% (prior lenalidomide). The safety profile in the prior lines subgroups was qualitatively similar to that in the broader ENDEAVOR population. In RMM, outcomes are improved when receiving treatment with carfilzomib compared with bortezomib, regardless of the number of prior therapy lines or prior exposure to bortezomib or lenalidomide. © 2017 Macmillan Publishers Limited, part of Springer Nature.

Notes:

Export Date: 18 February 2017References: Van De Donk, N.W., Lokhorst, H.M., Dimopoulos, M., Cavo, M., Morgan, G., Einsele, H., Treatment of relapsed and refractory multiple myeloma in the era of novel agents (2011) Cancer Treat Rev, 37, pp. 266-283;(2016) NCCN Guidelines Multiple Myeloma (Version 2, , http://www.nccn.org/professionals/physician_gls/f_guidelines.asp, National Comprehensive Cancer Network cited October 2015; Mohty, B., El-Cheikh, J., Yakoub-Agha, I., Avet-Loiseau, H., Moreau, P., Mohty, M., Treatment strategies in relapsed and refractory multiple myeloma: A focus on drug sequencing and 'retreatment' approaches in the era of novel agents (2012) Leukemia, 26, pp. 73-85; Kurtin, S.E., Relapsed or relapsed/refractory multiple myeloma (2013) J Adv Pract Oncol, 4, pp. 5-14; Durie, B.G., Moreau, P., Sonneveld, P., Morgan, G.J., Lahuerta, J.J., Beksac, M., Regional differences in the treatment approaches for relapsed multiple myeloma: An IMF study (2012) J Clin Oncol, 30. , abstr 8095; Kumar, S.K., Therneau, T.M., Gertz, M.A., Lacy, M.Q., Dispenzieri, A., Rajkumar, S.V., Clinical course of patients with relapsed multiple myeloma (2004) Mayo Clin Proc, 79, pp. 867-874; Kumar, S.K., Lee, J.H., Lahuerta, J.J., Morgan, G., Richardson, P.G., Crowley, J., Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study (2012) Leukemia, 26, pp. 149-157; McBride, A., Klaus, J.O., Stockerl-Goldstein, K., Carfilzomib: A second-generation proteasome inhibitor for the treatment of multiple myeloma (2015) Am J Health Syst Pharm, 72, pp. 353-360; Siegel, D.S., Martin, T., Wang, M., Vij, R., Jakubowiak, A.J., Lonial, S., A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma (2012) Blood, 120, pp. 2817-2825; Stewart, A.K., Rajkumar, S.V., Dimopoulos, M.A., Masszi, T., Spicka, I., Oriol, A., Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma (2015) N Engl J Med, 372, pp. 142-152; Dimopoulos, M.A., Moreau, P., Palumbo, A., Joshua, D., Pour, L., Hajek, R., Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): A randomised, phase 3, open-label, multicentre study (2016) Lancet Oncol, 17, pp. 27-38; Durie, B.G., Harousseau, J.L., Miguel, J.S., Blade, J., Barlogie, B., Anderson, K., International uniform response criteria for multiple myeloma (2006) Leukemia, 20, pp. 1467-1473; Khan, M.L., Stewart, A.K., Carfilzomib: A novel second-generation proteasome inhibitor (2011) Fut Oncol (London, England), 7, pp. 607-612; Kuhn, D.J., Chen, Q., Voorhees, P.M., Strader, J.S., Shenk, K.D., Sun, C.M., Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma (2007) Blood, 110, pp. 3281-3290; Sood, R., Carloss, H., Kerr, R., Lopez, J., Lee, M., Druck, M., Retreatment with bortezomib alone or in combination for patients with multiple myeloma following an initial response to bortezomib (2009) Am J Hematol, 84, pp. 657-660; Petrucci, M.T., Giraldo, P., Corradini, P., Teixeira, A., Dimopoulos, M.A., Blau, I.W., A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma (2013) Br J Haematol, 160, pp. 649-659; Attal, M., Lauwers-Cances, V., Marit, G., Caillot, D., Moreau, P., Facon, T., Lenalidomide maintenance after stem-cell transplantation for multiple myeloma (2012) N Engl J Med, 366, pp. 1782-1791; Dimopoulos, M.A., Delforge, M., Hajek, R., Kropff, M., Petrucci, M.T., Lewis, P., Lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in newly diagnosed multiple myeloma patients aged 65 years or older: Results of a randomized phase III trial (2013) Haematologica, 98, pp. 784-788; McCarthy, P.L., Owzar, K., Hofmeister, C.C., Hurd, D.D., Hassoun, H., Richardson, P.G., Lenalidomide after stem-cell transplantation for multiple myeloma (2012) N Engl J Med, 366, pp. 1770-1781; Palumbo, A., Hajek, R., Delforge, M., Kropff, M., Petrucci, M.T., Catalano, J., Continuous lenalidomide treatment for newly diagnosed multiple myeloma (2012) N Engl J Med, 366, pp. 1759-1769; Benboubker, L., Dimopoulos, M.A., Dispenzieri, A., Catalano, J., Belch, A.R., Cavo, M., Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma (2014) N Engl J Med, 371, pp. 906-917

Website