White Paper Predicts: with Continued, Specific Efforts, Cancer Can Become Chronic & Manageable by 2022

] ] [ 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

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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 It Work” Most Emailed and “Inside Look: First Oncology Medical Home” by Lola Butcher, 4/25/12 issue. • “Indications that Cetuximab & Erlotinib May Be Effective for Glioblastoma,”

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➞HEMATOLOGIC cumulative incidence of major molecular imatinib at 24 months of follow-up MALIGNANCIES response (bcr/abl less than or equal to (P = 0.019)� Event-free survival was continued from page 7 0.1%) at 26 months was 68 percent on similar in the two arms of the study. the dasatinib arm, and 55 percent on Nicolini et al presented data on encephalopathy. Two patients had to stop the imatinib arm; 84 percent of patients subcutaneous omacetaxine mepesuccinate the treatment on account of CNS adverse on the dasatinib arm and 64 percent of in patients with chronic-phase or oncology times events. patients on the imatinib arm had suppres- accelerated-phase CML resistant/intol- Jabbour et al presented results with sion of the bcr/abl to less than or equal to erant to two or three approved tyrosine inotuzumab ozogamicin, a CD22 mono- 10 percent at three months. kinase inhibitors (Abstract 6513). This clonal antibody conjugated to calicheami- In an exploratory analysis, deeper first-in-class reversible transient inhibitor “At a clinical cin in patients with relapsed/refractory molecular response at three months was of protein elongation showed a major leukemia (Abstract 6501). Fourteen out associated with a higher probability of cytogenetic response rate of 16.2 and science symposium of 27 patients (52%) had a response, with progression-free and overall survival and 11 percent in patients resistant to two on immunotherapy three complete remissions, eight CRPs decreased transformation to accelerated or three PKIs, respectively. The median (complete remission without total platelet and blast phase. progression-free survival was 10.5 months for myeloma, there recovery), and three CRIs (CR with An update with three-year follow- and 6.5 months in the two cohorts, incomplete count recovery) observed. up from the ENESTnd trial of nilotinib respectively. were presentations Eleven out of 27 patients (41%) were versus imatinib in patients with newly on three different rendered MRD-negative with therapy. The diagnosed CML (Abstract 6509) contin- Chronic Lymphocytic Leukemia majority of side effects were grade 1 to 2, ued to show superiority for nilotinib over (CLL) monoclonal antibodies with the grade 3 to 4 adverse events being imatinib, with 73 percent of patients on Byrd et al presented interim results of a drug fever in four patients and elevated the nilotinib at 300 mg p.o. b.i.d. arm phase IB/II study of the Bruton’s tyrosine in development for the transaminases in two patients. being in a major molecular remission, kinase (BTK) inhibitor ibrutinib (PCI- disease—siltuximab, compared with 53 percent on the imatinib 32765) in treatment-naïve CLL patients Chronic Myelogenous Leukemia arm (P < 0.0001). (Abstract 6507). Ibrutinib was given for bortezomib, and (CML) Progression to accelerated/blast phase treatment-naïve CLL/SLL patients aged Cortes et al presented results from the of disease, including events after the 65 years or older in two separate cohorts everolimus.” PACE (Ponatinib Ph positive ALL and discontinuation continued to be lower at 420 mg per day or 840 mg per day until CML Evaluation) trial in patients resistant on the nilotinib arm compared with the disease progression. to or intolerant of dasatinib on nilotinib or imatinib arm. An overall response rate of 81 percent with the p351I mutation (Abstract 6503). in 26 patients treated at the 420 mg This study enrolled 449 patients in a phase per day dose, and 40 percent in the five II trial with this oral pan bcr/abl tyrosine “Phase IB/II studies of patients who received the 840 mg per kinase inhibitor. ibrutinib in combination day dose, was noted. Three of 26 pa- A major cytogenetic response was seen tients (12%) achieved a complete remis- in 49 percent of patients with chronic with ofatumumab and sion at 420 mg per day, with a median myelogenous leukemia in chronic phase follow-up of 14.4 months. No complete who were relapse/intolerant to dasatinib with bendamustine remissions were seen at the dose of 840 mg or nilotinib, and in 70 percent of patients and rituximab relapsed per day with 7.4 months of follow-up in with T531I mutation in chronic phase; that cohort of patients. 37 percent of patients in the relapsed/ and refractory CLL/ Treatment resulted in a transient surge intolerant cohort and 66 percent of pain peripheral blood lymphocyte counts tients in the T351I mutation cohort SLL showed high rates with rapid resolution of lymph nodes, achieved a complete cytogenetic response. of overall response of suggesting an effect on the microenviron- Major molecular responses were seen in ment. The drug was well tolerated with the 23 and 50 percent of patients, respectively. 100 and 90 percent, major toxicities being gastrointestinal, but Overall, the median time to major cytoge- few grade 3 events were seen, and there Hyperlinks! netic response was 12 weeks. Most toxici- respectively.” were no grade 4 toxicity events. ties were grade 1 to 2 in severity. The major Phase IB/II studies of ibrutinib in ccess the hyperlinks grade 3 or greater toxicity was an elevation An update of the BELA trial of combination with ofatumumab (Jaglowski A(shown in grey) in this in lipase seen in 10 percent of patients. bosutinib versus imatinib in patients with et al, Abstract 6508) and ibrutinib with article and throughout Hochhaus et al presented three-year newly diagnosed CML after 30 months of bendamustine and rituximab (O’Brien et the issue by reading it follow-up data from the DASISION follow-up (Abstract 6512) presented by al, Abstract 6515) in patients with on OT’s free iPad app: trial comparing dasatinib with imatinib Gambacorti-Passerini showed cumulative relapsed and refractory CLL/SLL showed http://bit.ly/OT-iPadApp in patients with newly diagnosed CML major molecular response rates of 59 per- high rates of overall response of 100 and O in chronic phase (Abstract 6504). The cent for bosutinib and 49 percent for 90 percent, respectively. T