Brian Dinh, PharmD
The University of Oklahoma College of Pharmacy
Oklahoma City, OK
Lisa A. Raedler, PhD, RPh
Acute Myeloid Leukemia
Efficacy outcomes in acute myeloid leukemia (AML) are poorer with advanced age and the presence of FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD). Quizartinib is an oral FLT3 inhibitor with activity against ITD-mutant and wild-type FLT3. Two studies of quizartinib in patients with AML were presented at EHA. In both studies, quizartinib was administered once daily as an oral solution in 28-day treatment cycles.1,2
At the 2013 EHA meeting, Hartmut Döhner, MD, University Hospital of Ulm, Ulm, Germany, and colleagues presented “Efficacy and safety of quizartinib (AC220) in patients aged ≥60 years with FLT3-ITD–positive relapsed/refractory acute myeloid leukemia (AML).” This phase 2 study enrolled 110 patients with AML aged ≥60 years, of whom 54 patients were aged ≥70 years. All patients were FLT3-ITD mutation-positive, and had either relapsed within 1 year or were refractory to first-line chemotherapy.1
After a median of 14.1 weeks of quizartinib treatment, 57% of AML patients ≥60 years of age had a composite complete remission (CRc), including 3 complete remissions (CRs), 4 CRs with incomplete platelet recovery (CRp), and 56 CRs with incomplete hematologic recovery (CRi). Median overall survival (OS) in patients ≥60 years of age was 25.3 weeks, with 16 patients (15%) surviving more than 52 weeks. Among patients aged ≥70 years, the median duration of treatment was 14.9 weeks, and 57% had a CRc (1 CR, 3 CRp, 27 CRi).1
Common grade 3 or 4 treatment-related adverse events associated with quizartinib included anemia (25%), febrile neutropenia (22%), thrombocytopenia (12%), transient QT interval prolongation (10%; no grade 4 events), and neutropenia (10%). For 20 patients (18%), these adverse events resulted in quizartinib discontinuation.1
The data show that quizartinib treatment in elderly FLT3-ITD–positive patients, even those aged ≥70 years and those with chemotherapy-resistant AML, resulted in high response rates and promising survival.1
Also at the EHA meeting, Mark Levis, MD, Johns Hopkins University, Baltimore, Maryland, reported the results of a phase 2 trial designed to assess the efficacy of quizartinib monotherapy in FLT3-ITD–positive patients with AML who were relapsed or refractory to second-line, salvage chemotherapy, or relapsed after hematopoietic stem cell transplantation (HSCT).2
In this study of 136 patients with AML who were at least 18 years of age, the CRc rate was 46% (5 CR, 2 CRp, and 55 CRi), with a median duration of CRc of 10.6 weeks. Median OS was 24.0 weeks. Among patients who were refractory to their last AML therapy, 47% achieved a CRc with quizartinib.2
Quizartinib was discontinued for HSCT in 47 patients (35%); 44 of these 47 patients (94%) had at least a partial response (PR)–2 CRp, 24 CRi, and 18 PR–on quizartinib. Eight of these 47 patients (17%) had received previous HSCT. Most of the 39 patients (82%) who did not receive previous HSCT were refractory to second-line AML therapy.2
The median OS was 41.5 weeks for patients who achieved a CRc (N = 26) prior to HSCT and 29.0 weeks for patients with PR (N = 18). The 1-year survival rate was 39% for both response groups. Patients with a CRc (N = 36) or PR (N = 20), but no HSCT, had a median OS of 24.5 weeks and 20.9 weeks, respectively, and 1-year survival rates of 25% and 5%, respectively. Of 27 patients with OS of more than 52 weeks, 17 (63%) underwent HSCT.2
Dr Levis concluded that quizartinib demonstrated notable activity and very promising survival in patients with relapsed or refractory FLT3-ITD–positive AML, particularly for responders who subsequently received HSCT.2
Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of functionally incompetent lymphocytes. Combination chemotherapy regimens used in CLL typically include nucleoside analogues (fludarabine), alkylating agents (cyclophosphamide), and biologics (alemtuzumab, ofatumumab, rituximab). Allogeneic stem cell transplantation is the only known curative therapy. Novel therapies under investigation in CLL include monoclonal antibodies, kinase inhibitors, and cytotoxic agents. Key presentations and posters on the results of trials in patients with CLL are summarized in the Table.
Chronic Myeloid Leukemia
Hematologists continue to debate the selection of first-line tyrosine kinase inhibitor (TKI) therapy for patients with chronic myeloid leukemia (CML). Long-term data are valuable in understanding the relative efficacy and safety of TKIs in these patients. A large, open-label, phase 3 trial known as ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients) evaluated the second-generation TKI nilotinib in 846 adults with newly diagnosed, Philadelphia chromosome–positive (Ph+) CML in chronic phase (CML-CP). Initial results of this trial were published in 2010 and demonstrated superior rates of major molecular response (MMR), deeper molecular responses (MR), and reduced rates of progression for nilotinib compared with imatinib.8
During the 2013 EHA meeting, Andreas Hochhaus, MD, Universitätsklinikum Jena, Jena, Germany, presented updated efficacy and safety data for nilotinib and imatinib after a minimum of 4 years of follow-up. Nilotinib continued to demonstrate significantly higher rates of MMR, MR,4 and MR4,5 (BCR-ABL transcript level ≤0.1%, ≤0.01%, and ≤0.0032%, respectively) versus imatinib. Patients on the 2 nilotinib arms of the ENESTnd trial had significantly lower rates of progression to accelerated phase (AP) or blast crisis (BC) on the study, including follow-up after discontinuation of treatment, compared with patients receiving imatinib. The 4-year OS rates were 94.3%, 96.7%, and 93.3% for nilotinib 300 mg given orally twice daily, nilotinib 400 mg twice daily, and imatinib 400 mg once daily, respectively.9
There were no new safety signals for nilotinib. The safety profiles of both drugs were consistent with those previously reported, with few newly occurring hematologic or biochemical abnormalities, or cardiac or vascular events in any treatment arm. Treatment-emergent BCR-ABL mutations were less common in patients receiving nilotinib compared with imatinib. Two patients had newly emergent mutations in year 4.9
Dr Hochhaus concluded that, after a minimum of 4 years of follow-up, significantly higher rates of molecular response with nilotinib continued, as well as lower rates of progression to AP or BC, and fewer treatment- emergent BCR-ABL mutations relative to imatinib. These data provide additional support for the use of nilotinib as first-line therapy in patients with newly diagnosed Ph+ CML-CP.9
In estrogen receptor–positive (ER+) early-stage breast cancer, the clinical value of tamoxifen given for 5 years is well established–it reduces breast cancer death rates by about one third throughout years 0 to 14. To assess the clinical value of 10 years of tamoxifen, Richard Gray, MD, MSc, University of Oxford, Oxford, United Kingdom, and his colleagues conducted one of the largest trials in breast cancer, the Adjuvant Tamoxifen: To Offer More? (aTTom) trial. From 1991 to 2005, this trial enrolled 6953 women with ER+ (N = 2755), or ER untested (4198, estimated 80% ER+ if status known) invasive breast cancer from 176 cancer centers in the United Kingdom. After 5 years of tamoxifen, patients were randomized to either stop tamoxifen or continue tamoxifen to year 10. Patient compliance, breast cancer recurrence, mortality, and hospital admissions data were recorded each year.10
Dr Gray presented the results of the aTTom study in a plenary session at the 2013 ASCO meeting. This trial showed that the use of tamoxifen for a total of 10 years significantly reduced breast cancer recurrence (P = .003) and breast cancer mortality (P = .05), and reduced overall mortality (P = .1). Mortality unrelated to breast cancer was unaffected.10
The aTTom researchers concluded that, in ER+ disease, receipt of tamoxifen for 10 years rather than 5 years produces further reductions in disease recurrence from year 7 onward and in breast cancer mortality after year 10. Considered together with the reduction in breast cancer deaths seen in trials of 5 years of tamoxifen compared with no tamoxifen, these results indicate that 10 years of adjuvant tamoxifen, compared with no tamoxifen, reduces breast cancer deaths by approximately one third in the first 10 years following diagnosis and by one half subsequently.10
While the role of tamoxifen in ER+ breast cancer is now well established, there is disagreement over whether certain antidepressants, such as paroxetine, can reduce tamoxifen’s effectiveness. Previous studies have been limited by small sample sizes or poor medication measurement.11
At MASCC/ISOO 2013, Reina Haque, PhD, of Kaiser Permanente Southern California, Pasadena, presented results of a study that examined whether taking tamoxifen and antidepressants concomitantly was associated with an increased risk of subsequent breast cancer.11
In this study, data were collected from 16,887 breast cancer patients (stages 0-2) who were treated with tamoxifen and who participated in large healthcare plans in California. Women were followed through breast cancer relapse, health plan disenrollment, death, or study’s end. Researchers learned that a total of 2946 women developed subsequent breast cancer during the 14-year study period. Of the 16,887 women, approximately half had used antidepressants. A small nonsignificant increased risk of subsequent breast cancer was observed in women who concurrently used paroxetine and tamoxifen in the first year, but the risk attenuated with longer tamoxifen duration. No such trend was found with other antidepressants.11
One of three highlighted presentations at the 2013 AUA annual meeting was given by Timothy Daskivich, MD, of the University of California Los Angeles (UCLA): “Age, comorbidity, and risk of other-cause mortality: fourteen-year results from the Prostate Cancer Outcomes Study (PCOS).” This study sampled 3183 men with nonmetastatic prostate cancer from PCOS to define the risk of other-cause mortality associated with age and comorbidity in a population-based cohort of men with early-stage disease. Comorbidity was measured as the number of the following prespecified medical conditions present at diagnosis: diabetes, stroke, myocardial infarction, ulcer, congestive heart failure, angina, liver disease, arthritis, hypertension, depression, inflammatory bowel disease, and chronic lung disease. The authors conducted competing risk analyses of other-cause mortality by comorbidity and cancer-specific mortality by tumor risk. The study results showed that 14-year cumulative other-cause mortality was 24%, 33%, 46%, and 57% for men with comorbidity counts 0, 1, 2, and 3 or more, respectively. With each decade increase in age, the subhazard of other-cause mortality associated with comorbidity count doubled. In men with 3 or more comorbidities, 10-year other-cause mortality rates were 26%, 40%, and 71% for those aged ≤60, 61 to 74, and ≥75 years at diagnosis, respectively (see Figure). These results may help eliminate overtreatment that results from poor understanding of life expectancy associated with comorbidity in older men with early-stage prostate cancer.12
The second highlighted presentation was by Fred Saad, MD, of the University of Montreal Hospital Centers: “Abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy–interim analysis of the COU-AA-302 phase 3 trial.”13 Abiraterone acetate is a first-in-class inhibitor of cytochrome P450 C17, a critical enzyme in extragonadal and testicular androgen synthesis.14 Initially, abiraterone plus low-dose prednisone improved survival in patients with metastatic castration-resistant prostate cancer (mCRPC) and was approved for second-line therapy after docetaxel therapy. Recent studies have led to its approval for use prior to chemotherapy for mCRPC. The COU-AA-302 phase 3 trial compares abiraterone/prednisone and prednisone in asymptomatic or mildly symptomatic patients with progressive mCRPC and no prior chemotherapy. A total of 1088 patients were stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1) and then randomized 1:1 to abiraterone or placebo plus low-dose prednisone. Prespecified analyses of OS (35.3 months vs 30.1 months; P = .015) and radiographic PFS (16.5 months vs 8.3 months; P <.0001) favored the abiraterone/prednisone arm. Grade 3 or 4 hypertension, hypokalemia, and liver enzyme elevations were more common in the abiraterone/prednisone arm.13
The last highlighted oral presentation at AUA was given by Kazuhiro Matsumoto, MD, of Saiseikai Central Hospital, Toyko, Japan: “Can antiandrogen withdrawal therapy be performed safely for aggressive prostate cancer?” This study was designed to examine the safety of antiandrogen withdrawal (AAWD) as a potential therapeutic maneuver for treating patients with CRPC who have also received a combined antiandrogen therapy. AAWD was performed in 95 patients, of whom 68 patients had previously received bicalutamide and 27 patients had received flutamide. In 29 of 95 patients (30.5%), the serum prostate-specific antigen (PSA) level decreased after AAWD. In 11 patients (10.5%), there was a greater than 50% decrease from the baseline serum PSA level. The median response duration was 4 months in these 29 patients who responded. In the 66 nonresponders, the mean PSA doubling time (PSADT) before and after AAWD was 7.7 months and 6.2 months, respectively. A shortening of PSADT after AAWD was observed in 37 patients (38.9%) who were nonresponders. Univariate and multivariate analyses were performed to identify predictors of shortened PSADT after AAWD. The results indicated that patients with a short PSADT (aggressive disease) before AAWD had a low risk that PSADT would shorten following AAWD. The authors concluded that AAWD should be considered for all patients with CRPC before embarking on the next therapeutic maneuver.15
At ASCO 2013, Matthew Smith, MD, Massachusetts General Hospital Cancer Center, Boston, presented “Efficacy and safety of enzalutamide (ENZA) monotherapy in hormone-naive prostate cancer (HNPC).” Enzalutamide is an oral androgen receptor (AR) inhibitor with high AR-binding affinity that prevents nuclear translocation, shows no DNA binding, and induces apoptosis. The agent was approved by the US Food and Drug Administration after demonstrating prolonged OS in patients with mCRPC who had received docetaxel. This phase 2, open-label, single-arm trial included 67 patients with HNPC and a median age of 73 years. At baseline, patients had a noncastrate testosterone level of at least 230 ng/dL, a PSA of at least 2 ng/mL, an ECOG performance status of 0, and a life expectancy of at least 1 year. All patients were treated with enzalutamide daily for 25 weeks. The primary end point of the study was PSA response, defined as at least an 80% decline in PSA. At 25 weeks, the PSA response was 93% and the median PSA decrease was 99.6%. The primary end point was achieved in 62 of the 67 patients. All common adverse events were grade 1 or 2 and included gynecomastia, fatigue, nipple pain, hot flush, diarrhea, and nausea.16
Dr Smith summarized the study stating, “The results compare favorably with that expected with standard androgen deprivation therapy. In contrast to castration, enzalutamide monotherapy was associated with stable bone mineral density and only modest changes in serum cholesterol and triglycerides.”16
Diffuse large B-cell lymphoma (DLBCL) has 2 molecular subtypes: activated B cell-like (ABC) and germinal center B cell-like (GCB). Survival in the ABC subtype is sustained by “chronic active” B-cell receptor (BCR) signaling, making it very difficult to treat. At the 2013 EHA meeting, Wyndham Wilson, MD, PhD, National Cancer Institute, Bethesda, Maryland, presented “The Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), has preferential activity in the activated B cell-like (ABC) subtype of relapsed/refractory DLBCL: interim phase 2 results.” This international, multicenter, phase 2 study of single-agent ibrutinib tested the hypothesis that ibrutinib would be more active in ABC than in GCB due to targeted inhibition of the BCR signaling pathway. A total of 70 patients were enrolled and treated with ibrutinib orally once a day until disease progression. In the ABC patients, responses were observed in 12 of 29 patients for an overall response rate (ORR) of 41% (complete response [CR] 17%, partial response [PR] 24%), In the GCB patients, ORR was 5% (1/20) with no CRs. Median OS was 9.8 months for the ABC subtype and 3.4 months for the GCB subtype. These interim results showed that ibrutinib had a clinically meaningful ORR in relapsed/refractory ABC DLBCL, but not in the GCB subtype.17
While the majority of patients with Hodgkin lymphoma are cured with treatment, the management of patients with primary refractory Hodgkin lymphoma represents a significant clinical challenge. During the 2013 EHA congress, Dr M. David of the Royal Shrewsbury Hospital, Shrewsbury, United Kingdom, presented “Development of a prognostic scoring system for primary refractory Hodgkin’s lymphoma treated with high-dose chemotherapy and autologous stem cell transplantation” (ASCT). Thirteen prognostic factors were analyzed in 45 patients with primary refractory Hodgkin lymphoma treated with salvage chemotherapy and subsequent high-dose chemotherapy and ASCT. The goal was to create a prognostic scoring system that is specific for primary refractory Hodgkin lymphoma. Analyzed prognostic factors included age, sex, Ann Arbor stage, histologic subtype, presence of B symptoms, presence of bulky disease, radiotherapy, type of conditioning regimen, number of previous treatment lines, response before ASCT, time interval between diagnosis and ASCT, lactate dehydrogenase, and serum albumin. Based on the analysis, 5 adverse prognostic factors were identified as significant (P <.05): (1) Ann Arbor stage (stage 4 disease), (2) number of previous treatment lines (≤3, >3), (3) response before ASCT (progression, stable disease, response), (4) time interval between diagnosis and ASCT (≤18 months, > 18 months), and (5) serum albumin (≤35 g/L, >35 g/L). A prognostic scoring system was constructed from these 5 significant prognostic factors.
Patients with 0 or 1 adverse prognostic factor were defined as a low-risk group. Those with 2 or 3 adverse prognostic factors were in a medium-risk group. Those with >3 adverse prognostic factors were defined as an ultrahigh-risk group. A highly significant difference (P <.001) in OS was observed for patients in each of the 3 prognostic groups when compared with either of the other 2 groups. Future research in larger cohorts of patients with primary refractory Hodgkin lymphoma is needed to validate these findings.18
At MASCC/ISOO 2013, Richard Gralla, MD, Albert Einstein College of Medicine, Bronx, New York, presented “Novel all-oral combination of netupitant plus palonosetron (NEPA) for preventing CINV with highly emetic chemotherapy: a randomized study exploring maximally convenient and effective regimens.”19 NEPA is an all-oral combination of netupitant, a long-acting NK1 receptor antagonist, and palonosetron, a pharmacologically distinct 5-HT3 receptor agonist. The combination was developed to improve antiemetic control, avoiding chemotherapy-induced nausea and vomiting (CINV), as well as enhance the convenience of administering antiemetic prophylaxis targeted at dual molecular pathways involved in emesis.20 The study presented by Dr Gralla was designed to determine effective netupitant doses in the combination. A total of 694 chemotherapy-naive patients receiving cisplatin-containing chemotherapy regimens were randomized in the double-blind study to receive 1 of 3 doses of netupitant plus palonosetron 0.5 mg or palonosetron 0.5 mg on day 1. All patients received oral dexamethasone on days 1 to 4. The combination known as NEPA300, netupitant 300 mg plus palonosetron 0.5 mg, demonstrated the best overall CR (complete response: no emesis, no rescue) and acute CR rates. The authors concluded that NEPA300 is especially suited for further trials using maximally convenient single-dosing strategies.19
Also during MASCC/ISOO 2013, Bernardo Rapoport, MD, of The Medical Oncology Centre of Rosebank, Johannesburg, South Africa, presented “Supportive care highlights since MASCC 2012: febrile neutropenia.”21 The main session reviewed the second set of ASCO guidelines for febrile neutropenia (FN): “Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology Practice Guideline.”22 Two of these guidelines included recommendations for outpatient management of FN patients who have a low risk of complications, and the use of prophylactic antibiotics and antifungals for patients anticipated to be severely neutropenic (absolute neutrophil count [ANC] ≤100/mcL) for 7 days or longer.22 Complete management of FN in the outpatient setting requires proper assessment (eg, MASCC scoring index, Talcott’s rules), observation by qualified healthcare professionals, and ability to follow up with access to healthcare professionals. The potential advantages of outpatient care are increased convenience for patients and family, reduced cost of care, and decreased hospital-acquired infections. Dr Rapoport concluded that, although outpatient antibiotic therapy for FN is widely used, there is a lack of large, randomized trials to further characterize patients for whom outpatient antibiotic therapy for FN is safe. Treatment for FN should be individualized based on each patient’s risk of complications.21
Jeffrey Crawford, MD, Duke University Medical Center, Durham, North Carolina, presented “Effectiveness of pegfilgrastim prophylaxis for reducing the risk of febrile neutropenia in patients with advanced stage solid tumors.”23 Patients with advanced cancer receiving chemotherapy are at risk for developing FN; however, NCCN guidelines do not clearly recommend granulocyte colony-stimulating factor (GCSF) for these patients. Dr Crawford and colleagues pooled patients from 3 Amgen-sponsored placebo-controlled trials (placebo vs pegfilgrastim prophylaxis): a phase 3 trial in patients with breast cancer,24 and a phase 2 and a phase 3 trial in patients with colorectal cancer.25,26 A total of 1823 patients with advanced cancer were treated with chemotherapy and had intermediate risk for FN. Results of the pooled analysis showed that pegfilgrastim use significantly reduced the incidence of grade 3/4 FN by 4-fold compared with placebo (P <.001).23
At the 2013 ASCO meeting, Oleg Gladkov, MD, Chelyabinsk Regional Clinical Oncology Center, Chelyabinsk, Russia, presented “Efficacy and safety of balugrastim in chemotherapy-induced neutropenia: integrated analysis of two randomized phase III studies.” Balugrastim is a fully human recombinant fusion protein composed of serum albumin and GCSF that is administered once each chemotherapy cycle. Dr Gladkov and colleagues presented a combined analysis of 2 double-blind, randomized phase 3 studies comparing efficacy and safety of balugrastim and pegfilgrastim in patients with breast cancer who were receiving myelosuppressive chemotherapy. Patients were treated with up to 4 cycles of doxorubicin followed by docetaxel. During each cycle, patients received a single subcutaneous injection of GCSF approximately 24 hours after chemotherapy administration. The primary end point for both studies was duration of severe neutropenia (DSN) in cycle 1. A total of 469 patients were randomized to receive balugrastim (N = 235) or pegfilgrastim (N = 236). Balugrastim was found to be noninferior to pegfilgrastim for reduction in DSN. The mean DSN in cycle 1 was 1.1 ± 1.11 days in patients receiving balugrastim and 1.0 ± 1.14 days in patients receiving pegfilgrastim. Patients treated with balugrastim had a significantly shorter time to ANC recovery in cycle 1 compared with pegfilgrastim (2.0 days vs 2.3 days; P = .015). Safety profiles were similar for both drugs, with the incidence of adverse events consistent with the underlying medical condition and administration of myelosuppressive chemotherapy. The authors concluded that balugrastim is a safe and effective alternative to pegfilgrastim for reducing DSN in patients with breast cancer who are receiving myelosuppressive chemotherapy.27
1. Döhner H, Perl A, Rousselot P, et al. Efficacy and safety of quizartinib (AC220) in patients aged ≥60 years with FLT3-ITD–positive relapsed/refractory acute myeloid leukemia (AML). Haematologica. 2013;98(suppl 1):233. Abstract S558.
2. Levis M, Cortes J, Perl A, et al. High response rate and bridging to hematopoietic stem cell transplantation with quizartinib (AC220) in patients with FLT3-ITD–positive relapsed/refractory acute myeloid leukemia (AML). Haematologica. 2013;98(suppl 1):17. Abstract P043.
3. Goede V, Fischer K, Humphrey K, et al. Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab (R) plus Clb versus Clb alone in patients with chronic lymphocytic leukemia (CLL) and preexisting medical conditions (comorbidities): final stage 1 results of the CLL11 (BO21004) phase 3 trial. Haematologica. 2013;98(suppl 1):237. Abstract S567.
4. Press release, July 24, 2013. Roche’s obinutuzumab (GA101) delayed disease progression longer than MabThera/Rituxan in people with one of the most common forms of blood cancer. http://www.roche.com/media/media_releases/med-cor-2013-07-24.htm. Accessed August 12, 2013.
5. Piris-Villaespesa M, Chavez J, Dalia S, et al. Updated results of a phase 2 study of lenalidomide and rituximab in relapsed/refractory chronic lymphocytic leukemia. Haematologica. 2013;98(suppl 1):46. Abstract P108.
6. Coutre S, Leonard J, Furman R, et al. Update on a phase 1 study of the selective PI3K-delta inhibitor, idelalisib (GS–1101) in combination with ofatumumab in patients with relapsed or refractory chronic lymphocytic leukemia. Haematologica. 2013;98(suppl 1):474. Abstract S1150.
7. Barrientos J, Leonard J, Furman R, et al. Phase 1B study of idelalisib (GS–1101) plus chlorambucil ± rituximab in patients with relapsed and refractory chronic lymphocytic leukemia (CLL). Haematologica. 2013;98(suppl 1):42. Abstract P100.
8. Saglio G, Kim D-W, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251-2259.
9. Hochhaus A, Saglio G, Larson R, et al. Nilotinib shows sustained benefit compared with imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML–CP): ENESTnd 4-year follow-up (F/U). Haematologica. 2013;98(suppl 1):298. Abstract P712.
10. Gray RG, Rea D, Handley K, et al. aTTom: long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol (ASCO Annual Meeting Abstracts). 2013; 31(suppl). Abstract 5.
11. Haque R, Shi J, Fletcher SW, et al. Tamoxifen & antidepressant drug interactions in a cohort of breast cancer survivors cared for in large healthcare delivery systems in California. Support Care Cancer. 2013;21(suppl 1):S205. Abstract MASCC-0586.
12. Daskivich TJ, Fan K-H, Koyama T, et al. Age, comorbidity, and risk of other-cause mortality: fourteen-year results from the Prostate Cancer Outcomes Study (PCOS). Presented at: American Urological Association Annual Meeting 2013; May 4-8, 2013; San Diego, CA. Abstract 58.
13. Saad F, Shore ND, Van Poppel H, et al. Abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy–interim analysis of the COU-AA-302 phase 3 trial. Presented at: American Urological Association Annual Meeting 2013; May 4-8, 2013; San Diego, CA. Abstract 713.
14. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138-148.
15. Matsumoto K, Hayakawa N, Ezaki T, et al. Can antiandrogen withdrawal therapy be performed safely for aggressive prostate cancer? Presented at: American Urological Association Annual Meeting 2013; May 4-8, 2013; San Diego, CA. Abstract 958.
16. Smith MR, Borre M, Rathenborg P, et al. Efficacy and safety of enzalutamide (ENZA) monotherapy in hormone-naive prostate cancer (HNPC). J Clin Oncol (ASCO Annual Meeting Abstracts). 2013;31(suppl). Abstract 5001.
17. deVos S, Wilson W, Gerecitano J, et al. The Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), has preferential activity in the activated B cell-like (ABC) subtype of relapsed/refractory (R/R) DLBCL: interim phase 2 results. Haematologica. 2013;98(suppl 1):490. Abstract S1180.
18. David M, Mozes R, Horvath E, et al. Development of a prognostic scoring system for primary refractory Hodgkin’s lymphoma treated with high-dose chemotherapy and autologous stem cell transplantation. Haematologica. 2013; 98(suppl 1):71. Abstract P162.
19. Gralla R, Rossi G, Rizzi G, et al. Novel all-oral combination of netupitant plus palonosetron (NEPA) for preventing CINV with highly emetic chemotherapy: a randomized study exploring maximally convenient and effective regimens. Support Care Cancer. 2013;21(suppl 1):S151. Abstract MASCC-0432.
20. Aapro M, Rizzi G, Borroni ME, et al. Phase 3 study of NEPA, a fixed-dose combination of netupitant (NETU) and palonosetron (PALO), versus PALO for prevention of CINV following moderately emetogenic chemotherapy (MEC). Support Care Cancer. 2013;21(suppl 1):S151. Abstract MASCC-0433.
21. Rapoport BL. Supportive care highlights since MASCC 2012: febrile neutropenia. Presented at: Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) 2013 International Symposium on Supportive Care in Cancer; June 27-29, 2013; Berlin, Germany.
22. Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology Practice Guideline. J Clin Oncol. 2013;3:794-810.
23. Crawford J, Reiner M, Dale D, et al. Effectiveness of pegfilgrastim prophylaxis for reducing the risk of febrile neutropenia in patients with advanced stage solid tumors. Support Care Cancer. 2013;21(suppl 1):S153. Abstract MASCC-0438.
24. Vogel CL, Wojtukiewicz MZ, Carroll RR, et al. First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol. 2005;23:1178-1184.
25. Hecht JR, Pillai M, Gollard R, et al. A randomized, placebo-controlled phase ii study evaluating the reduction of neutropenia and febrile neutropenia in patients with colorectal cancer receiving pegfilgrastim with every-2-week chemotherapy. Clin Colorectal Cancer. 2010;9:95-101.
26. Pinter T, Abella S, Cesas A, et al. Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC). Poster presented at: 2013 Gastrointestinal Cancers Symposium; January 24-26, 2013; San Francisco, CA. Abstract LBA445.
27. Gladkov O, Volovat CD, Barash S, et al. Efficacy and safety of balugrastim in chemotherapy-induced neutropenia: integrated analysis of two randomized phase III studies. J Clin Oncol (ASCO Annual Meeting Abstracts). 2013; 31(suppl). Abstract e17572.