] ] [ News ] Analysis ] Commentary ] Controversy ] July 10, 2012 Vol. 34 No. 13 oncology-times.com Publishing for O34 Years NCoLoGY The Independent TIMES Hem/Onc News Source White Paper Predicts: With Continued, Specific Efforts, Cancer Can Become Chronic & Manageable by 2022 BY PEGGY EASTMAN hat was the conclusion of the docu- Tment by representatives from AACR, the Personalized Medicine Coalition, and Feinstein Kean Healthcare, distributed­ at this conference­ . Read what John Mendelsohn, Siddartha Mukherjee, Laura Esserman, and others had to say. Page 22 Key Takeaways! Free Instant • Personal Picks—ASCO President SANDRA SWAIN Access to • Hematologic (ALL, CML, CLL, Plasma Cell Dyscrasias)—RAVI VIJ OT on Your • GU–WALTER STADLER iPad! • Lung Cancer – RENALDO MARTINS • Plus: JOE SIMONE on ASCO Past, Present, & Future Starting on p. 7 [ALSO] SHOP TALK ������������������������������������������������������������������������������������������4 ALL: Confirmation that Adolescents & Young Adults Do Better on Pediatric Protocols ����������������23 Metastatic Breast Cancer: T-DM1 Superior to Capecitabine-Lapatinib ����������������������������������������26 Platinum-Resistant Ovarian Cancer: Bevacizumab Extends Survival ����������������������������������������������28 ASTRO Leader HOWARD SANDLER on PSA Screening ����������������������������������������������������������30 Controlling Intractable Pain Resistant to Opiates ��������������������������������������������������������������������������31 Debating PFS vs. OS as Trial Endpoint ����������������������������������������������������������������������������������������32 Facebook.com/ @OncologyTimes PERIODICALS OncologyTimesNews 7 Best of ASCO 2012: Hematological Malignancies oncology times Plasma Cell Dyscrasias, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, & Chronic Lymphocytic Leukemia BY RAVI VIJ, MD • july 10, 2012 his year’s ASCO Annual Meeting was generally well tolerated, and a 2 mg/ ­anti-IL-6 ­monoclonal antibody, plus bort- had several exciting presenta- m2 dose was established as the MTD on a ezomib versus bortezomib alone in patients tions focusing on a variety of twice weekly regimen. with relapsed/refractory multiple­ myeloma ­hematological malignancies. This drug has been found to have a (Abstract 8018). Although there was a THere, I ­review what I consider the most much longer terminal half life of four to trend for an increase in overall­ response significant developments in plasma cell six days, in comparison to bortezomib, rates, only marginal and non­significant dyscrasias, acute lymphoblastic ­leukemia, and despite being a boronate, no grade effects on progression-free survival were • chronic myelogenous leukemia, and 3 or 4 peripheral neuropathy was noted. noted. oncology-times.com chronic lymphocytic leukemia. Six out of 53 patients achieved a partial Plesner et al reported encouraging response or better. preliminary efficacy data from a multi- Plasma Cell Dyscrasias In another presentation, Kumar et center phase I/II study of daratumumab, The oral session on plasma cell dys- al reported on once-weekly dosing of a CD38 monoclonal antibody, in patients RAVI VIJ, MD, is Associate crasias had three presentations look- MLN9708 in patients with relapsed/ with relapsed/refractory disease (Abstract Professor of Medicine in ing at combination therapies with the refractory disease (Abstract 8034). 8019). The MTD of the drug has not yet the Section of Stem Cell novel proteosome inhibitor carfilzomib. Here, the maximally tolerated dose was been established. However, seven out of Transplant and Leukemia Philippe Moreau et al (first author Brigitte 2.97 mg/m2. In addition, Richardson 29 heavily pretreated patients had a par- at Washington University Kolb) reported­ on a phase I/II study of reported on a regimen of MLN9708, tial response, and four patients achieved a School of Medicine in ­carfilzomib plus melphalan and ­prednisone given weekly in combination with le- minimal response. St. Louis. in elderly patients with de novo multiple nalidomide and dexamethasone, in Moreau et al presented data from myeloma (Abstract 8009). Despite the patients with ­previously untreated mul- a randomized phase II study of elotu- phase I /II nature of the trial, a very prom- tiple myeloma. The maximally tolerated zumab with lenalidomide and low-dose ising overall response of 89 percent with a dose was ­determined to be 2.97 mg/m2 dexamethasone in patients with relapsed 40 percent very good partial response rate (Abstract 8033). disease (Abstract 8020). A 92% response was seen. I, on behalf of my co-investigators, rate in patients treated at the 10 mg/kg Joseph Mikhael reported on a phase ­presented the outcomes of patients dose was reported, with the median pro- I/II trial of cyclophosphamide, carfilzo- ­refractory to lenalidomide and bort- gression-free survival not being reached mib, thalidomide, and dexamethasone ezomib, treated with pomalidomide at a median follow-up of 17.2 months in (CYCLONE) in patients with newly diag- with or without low-dose dexametha- that arm. nosed multiple myeloma (Abstract 8010). sone (MM002 study) (Abstract 8016). Ghobrial et al presented long-term An overall response rate of 96 percent with In this study an overall response rate results of a phase II trial of the oral a 75 percent very good partial response of 30 percent was seen with pomalido- mTOR inhibitor everolimus (RAD001) rate was noted. mide and low-dose dexamethasone in in relapsed or refractory Waldenström’s the intention-to-treat population with a macroglobulinemia. In this 60-patient ex- “This year’s ASCO Annual median progression-free survival of 3.8 perience, a response rate of over 50 percent A trial, though months, and a median overall survival of was noted in a patient population that had Meeting had several 14.4 months at the time of data cutoff in received a median of three prior therapies, early, of the novel exciting presentations April 2011. suggesting high single-agent activity with A preplanned subset analysis of this this drug. proteosome inhibitor focusing on a variety study showed that the response rates were carfilzomib combined similar in patients who were refractory to Acute Lymphoblastic Leukemia of hematological lenalidomide, refractory to bortezomib, Topp et al presented results of the with melphalan and malignancies.” and refractory to both lenalidomide and ­anti-CD19 BiTE blinatumomab in bortezomib, including dual-refractory adult patients with relapsed/refrac- prednisone in elderly And Andrzej Jakubowiak presented an patients who had had a prior stem cell tory B precursor acute lymphoblastic patients with de novo update on his trial combining carfilzomib transplant. ­leukemia (Abstract 6500). This ­bispecific with lenalidomide and dexamethasone In addition, Rossi et al reported impres- T-cell engager (BiTE) is designed multiple myeloma, with a stringent complete remission rate sive overall response rates and very good to direct cytotoxic T-cells to CD19- of 42 percent (Abstract 8011). partial response rates with a three-drug expressive cancer cells. With that given showed a very In an elegant commentary on the combination of clarithromycin, pomalid- as a continuous IV infusion, the trial promising overall above three abstracts, Robert Orlowski omide, and dexamethasone in relapsed/ established 5 mcg/m2 per day in week 1, ­concluded that upfront combination refractory disease (Abstract 8036). and then 15 mcg/m2 per day thereafter, response rate of 89% therapies with carfilzomib showed very ASCO 2012 also saw the first presenta- four weeks on and two weeks off, for up high rates of ­response, and it seemed that tion of the data from the PANORAMA 2 to five cycles as the dose for the extension and a very good the depth of response was improved with trial by Alsina et al (Abstract 8012). In this phase of the study. partial response rate better ­tolerability in terms of ­neuropathy. phase II study panobinostat in combina- A 72 percent CR/CRH (CR with However, he highlighted that firm tion with bortezomib and dexamethasone partial hematological recovery) rate was of 40%. ­conclusions versus bortezomib could in patients with relapsed and bortezomib demonstrated, with all but two of the not be drawn given the higher number of refractory multiple myeloma resulted in an responders achieving a complete mo- doses of carfilzomib administered per cycle overall response rate of 33 percent. lecular remission, with a median dura- in combination regimens. At a clinical science symposium ti- tion of complete ­hematological remission Another exciting compound in tled “Immunotherapy for Myeloma,” of 8.9 months, and a median survival of ­development includes the oral ­proteosome there were presentations on three dif- nine months. The major side effects were inhibitor MLN9708. Lonial et al pre- ferent monoclonal antibodies in devel- a cytokine release syndrome in three out sented data from a phase I study of opment for the disease. Orlowski et al of the 36 patients enrolled, and CNS twice-weekly dosing of this agent in pa- presented the results of a phase II ran- adverse events in six patients, including tients with relapsed and/or refractory mul- domized ­double-blind placebo-controlled three patients with ­seizures and three with tiple myeloma (Abstract 8017). The drug study comparing siltuximab, a chimeric continued on page 8 8 • “Practice Consolidation Moves to New Level,” by Lola Butcher, 6/10/12 issue. • “Medical Home for Oncology: COA Coordinating Plans to Make