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Highlights from ASH and SABCS

TOP - February 2015, Vol 8, No 1

The annual meetings of the American Society of Hematology (ASH) and the San Antonio Breast Cancer Symposium (SABCS) took place in December 2014, attracting US and international oncologists interested in the latest research on basic science and clinical medicine. Below is a selection of highlights from these meetings.

ASH Announces Second Choosing Wisely List

ASH announced its second list of 5 commonly used tests, treatments, and procedures in hematology that physicians and patients should discuss before routine use. This Choosing Wisely list adds to the first list of 5 practices that the society released in 2013 as part of the Choosing Wisely campaign, an initiative of the American Board of Internal Medicine (ABIM) Foundation that intends to spark conversations between patients and physicians about the risks and benefits of certain procedures.1 ASH’s new Choosing Wisely recommen dations include the following2:

  • Do not treat with an anticoagulant for >3 months in a patient with a first venous thromboembolism occurring in the setting of a major transient risk factor
  • Do not routinely transfuse patients with sickle-cell disease for chronic anemia or uncomplicated pain crisis without an appropriate clinical indication
  • Do not perform baseline or routine surveillance computed tomography scans in patients with asymptomatic, early-stage chronic lymphocytic leukemia
  • Do not test or treat for suspected heparin-induced thrombocytopenia (HIT) in patients with a low pretest probability of HIT
  • Do not treat patients with immune thrombocytopenic purpura in the absence of bleeding or a very low platelet count.

“Unnecessary treatments or tests not only add waste to the healthcare system, but in some cases, they also expose our patients to a risk of harm,” said Lisa Hicks, MD, of St. Michael’s Hospital and the University of Toronto, Ontario, Canada, and chair of the ASH Choosing Wisely Task Force. “ASH developed its second Choosing Wisely list to help hematologists manage the utilization and delivery of patient care resources, and ASH encourages hematologists to consider these recommendations in all facets of their work including patient care, teaching, innovation, and research.”

The guiding principle for the practices included in Choosing Wisely is to do no harm. Other principles guiding ASH’s choices for the lists include strength of evidence, aggregate cost, frequency, making recommendations within the purview of hematology, and potential impact in the field.3

Since the launch of the Choosing Wisely campaign in April 2012, more than 100 national and state medical specialty societies, regional health collaborative organizations, and consumer partners have joined this initiative aimed at providing appropriate care to patients.4 Consumer Reports has joined the effort, spreading the word to patients all over the country to stimulate discussions between physicians and patients about these and other practices.

1. Choosing wisely: an initiative of the ABIM Foundation. Accessed January 15, 2015.
2. American Society of Hematology. The ASH Choosing Wisely List. lines-Quality/502.aspx. Accessed January 15, 2015.
3. Choosing wisely: an initiative of the ABIM Foundation. Lists.­patient-lists/. Accessed January 15, 2015.
4. Choosing wisely: an initiative of the ABIM Foundation. Partners. Accessed January 15, 2015.

Dietary Fat Intake Studied in Patients with Early-Stage Breast Cancer

Women who limited their intake of dietary fat for 5 years after being diagnosed with early-stage breast cancer significantly reduced the mortality rate from all causes at 15 years of follow-up; this occurred specifically in women with hormone-unrelated cancer. No long-term effect of dietary fat reduction on mortality was observed in women with hormone receptor–positive breast cancer. The study was presented at the 2014 SABCS.

“These findings with respect to long-term influence of dietary lifestyle intervention on overall survival are mixed, but of potential importance,” said lead author Rowan T. Chlebowski, MD, PhD, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.

At 15 years, the overall mortality rate was lower in the dietary intervention group in the overall analysis compared with those in the control group, but the difference between the groups did not reach statistical significance (13.6% vs 17%, respectively). An exploratory analysis found a 36% reduction in mortality rates of women with estrogen receptor–negative breast cancer who lowered their dietary fat intake.

The Women’s Intervention Nutrition Study enrolled 2437 women with early-stage breast cancer who were treated with standard care at 39 centers in the United States. Ages at enrollment were between 48 and 79 years.

Of this group, 1597 had estrogen receptor–positive breast cancer, 478 had estrogen receptor–negative breast cancer, and 362 had estrogen receptor–negative/progesterone receptor–negative breast cancer. Within the first 6 months following diagnosis, women were randomized to a dietary fat intervention (N = 975) or control group (N = 1642).

In the intervention group, centrally trained dietitians counseled women for 8 biweekly individual sessions on how to implement a low-fat diet. Women were then contacted by dietitians every 3 months for 5 years. Women assigned to the dietary intervention group kept written records of their fat/gram intake. At 5 years, calorie intake was 8.9% lower in the intervention group, and these women lost about 6 pounds when compared with the control group.

Dr Chlebowski noted that human epidermal growth factor receptor 2 status was not assessed at the time this study was being conducted, but suggested that women with triple-negative breast cancer (estrogen receptor–negative/progesterone receptor–negative/and HER2-negative status) may also benefit from dietary fat reduction. In general, lowering dietary fat is a good idea for general health, he added.

Pediatric Regimens the New Standard for Adolescents and Young Adults with ALL

Early results of the large, prospective intergroup trial, C10403, demonstrate that a pediatric-inspired regimen improves event-free survival (EFS) and overall survival (OS) in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL). Many smaller studies have shown that AYAs have improved outcomes on pediatric regimens, but this is the first large data set to validate this practice. Two-year EFS was 66%, and 2-year OS was 78%.

“These results are a major improvement compared with 34% and 39%, respectively, in historical controls. This is a clear opportunity to improve care in AYAs with ALL,” said lead author Wendy Stock, MD, University of Chicago Medical Center in Illinois.

The study showed that the presence of a BCR-ABL1–like signature and aberrant CRLF2 expression were associated with worse EFS and OS; patients without these features had excellent EFS and OS, Dr Stock told listeners at the 2014 annual meeting of ASH.

The intergroup C10403 trial was undertaken by cooperative groups in North America to evaluate treatment with a pediatric intensive regimen delivered by adult hematologists/oncologists. Dr Stock presented the main results of the trial. Additional analysis of adherence and outcomes based on psychosocial factors will be presented in the future.

From 2007 to 2012, 296 AYA patients with ALL were treated. Median age was 24 years; 75% were white, 10% were African American, and 15% were Hispanic/Latino. Seventy-six percent had B-precursor ALL, and 24% had T-precursor ALL. Thirty-two percent of patients had a body mass index of ≥30, and 7% were morbidly obese.

The backbone of the pediatric-inspired regimen included intensified glucocorticoid, vincristine, and asparaginase, and more maintenance therapy. The regimen included remission induction and consolidation, interim maintenance, delayed intensification, and prolonged maintenance—2 years in women, and 3 years in men.

EFS was similar regardless of age-group or precursor B- or T-lineage. OS was significantly worse in obese patients, and significantly improved in patients with undetectable minimal residual disease (MRD).

Dr Stock and colleagues are planning to propose a successive US intergroup trial that should begin in 2015. The plans include use of the molecular signature of the disease to stratify patients and the addition of either a novel antibody or tyrosine kinase inhibitor to eradicate MRD and improve outcomes.

“This is a phenomenal achievement,” said Yoav Messinger, MD, a pediatric oncologist at Children’s Hospitals and Clinics of Minnesota in Minneapolis, and chairman of the session where these data were presented. “We have been waiting for a long time for these data, which put what we already know into a formalized protocol on a large-scale basis.”

Tinzaparin Is Safe and Effective in Reducing Risk for Recurrent Venous Thromboembolism

Tinzaparin, a low-molecular-weight heparin (LMWH), reduced the risk of recurrent venous thromboembolism (VTE) in patients with active cancer, lowered the risk of symptomatic deep vein thrombosis (DVT), and did not increase the risk of major bleeding despite full-dose use in the randomized, open-label CATCH study reported at the 2014 annual meeting of ASH by Agnes Lee, MD, University of British Columbia, Vancouver, Canada.

“Thrombosis is a common, deadly, and costly complication of cancer. Some tumors place patients at higher risk, including pancreatic, lung, co­lorectal, gastrointestinal, and brain cancer. As the largest randomized, controlled trial on the treatment of thrombosis among cancer patients, this study reinforces clinical guidelines supporting the use of LMWH instead of warfarin to prevent recurrent blood clots,” said Dr Lee.

Patients with cancer are at increased risk for VTE and DVT, which present major challenges for treatment, balancing the risks of bleeding with the benefits of blood clot dissolution. Current guidelines recommend the use of LMWH to reduce the risk of clotting—however, this recommendation was based on a single trial. Given the lack of confirmatory trials or trials of different medications, warfarin is commonly used as an anticoagulant in cancer patients.

CATCH enrolled 900 cancer pa­tients with DVT or pulmonary embolism at 165 different centers around the world to evaluate the efficacy and safety of tinzaparin versus warfarin. Patients were randomized to receive tinzaparin once daily for 6 months, or tinzaparin once daily for 5 to 10 days followed by 6 months of warfarin.

During treatment, 31 patients (6.9%) experienced recurrent VTE on tinzaparin versus 45 (10%) of the patients treated with warfarin, representing a 35% reduction in the risk of recurrent VTE. However, this difference was not statistically significant.

Tinzaparin reduced the risk of symptomatic DVT by 52% compared with the warfarin arm, and this difference was statistically significant (P = .04). Tinzaparin also reduced clinically relevant nonmajor bleeding (11% vs 16%, respectively; P = .03).

“This study validates the superiority of LMWH,” Dr Lee said. “Although LMWH is much more expensive than warfarin, there is no need for continual monitoring as there is with warfarin.”

Single-Agent Capecitabine Fails to Improve Outcomes in Elderly Patients with Breast Cancer

Adjuvant therapy with capecitabine plus ibandronate does not improve outcomes compared with ibandronate alone in elderly patients with moderate-to­-high-risk early­-stage breast cancer in the ICE (Ibandronate With or Without Capecitabine in Elderly Patients With Early Breast Cancer) study. Toxic effects of anthracyclines and taxanes would improve outcomes. The women included in this trial were not candidates for conventional chemotherapy with taxanes and anthracyclines. The hope was that an oral therapy free of the side effects of combination chemotherapy could improve outcomes.

Lead author of ICE, Gunter von Minckwitz, MD, University of Frankfurt, Germany, and chairman of the German Breast Group, said that capecitabine is frequently used in elderly patients who cannot tolerate the side effects of conventional chemotherapy—but these findings no longer support that practice.

Three-year invasive disease-free survival (DFS) was 85.4% for those who received the capecitabine/ibandronate treatment arm versus 84.3% in the ibandronate arm; 5-year invasive DFS was 78.8% versus 75%, respectively.

ICE was a prospective, randomized, multicenter trial that enrolled 1380 patients with node-positive or high- risk node-negative early breast cancer. Women aged ≥65 years were randomized in a 1:1 ratio to capecitabine plus ibandronate or ibandronate alone for 2 years of treatment. At the time the study was initiated, ibandronate was thought to have a protective effect against breast cancer.

Mean age was 71 years, and about 25% were aged 75 years or older. About 10% had a Charlson Comorbidity Index score of 2. One third of patients were receiving ≥3 medications for comorbidities. About 14% had triple-negative breast cancer, about 80% had hormone receptor–positive breast cancer, and about 70% were on aromatase inhibitors only.

Interestingly, ibandronate did not prevent bone-related events in this study. Fractures, surgery, and new osteoporosis—excluding bone metastases­occurred in 25% of the patients in the capecitabine/ibandronate group versus 24.7% receiving ibandronate alone. It did not make a difference whether ibandronate was given intravenously (about 35%) or orally (about 65%). Results of treatment were similar across all subgroups.

“These results, together with results of CALGB 49907, strongly support the use of combination chemotherapy in elderly patients,” Dr von Minckwitz said. CALGB 49907 compared capecitabine versus combination chemotherapy in elderly women and found that combination chemotherapy was superior and could be given to patients with a reasonable life expectancy.

“A patient has to be really unfit [for me to] not give her chemotherapy,” he added.

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