The American Society of Hematology (ASH) and the San Antonio Breast Cancer Symposium (SABCS) held back-to-back meetings in December 2013. The ASH annual meeting hosted approximately 20,000 attendees in New Orleans, Louisiana, where more than 5300 abstracts were presented, orally or as posters. About 7500 participants from more than 90 countries attended the breast cancer symposium. Below are selected brief highlights from these meetings.
Bisphosphonates Lower Risk of Recurrence and Death in Postmenopausal Early Breast Cancer
In postmenopausal women with early breast cancer, bisphosphonates in the adjuvant setting reduced the risk of recurrence in bone by 34% and breast cancer death by 17% according to a large meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group.
The risk reductions in bone recurrence and death with adjuvant bisphosphonates were observed in postmenopausal women regardless of estrogen receptor status, nodal status, and chemotherapy. Bisphosphonates had no effect on outcomes in premenopausal women.
“In addition to the 17% reduction in breast cancer–related mortality, adjuvant bisphosphonates led to an absolute reduction of 3.4% in all-cause mortality,” stated lead author Robert Coleman, MD, University of Sheffield, United Kingdom.
“These results are likely to be practice changing, leading to a new option for standard of care,” said Peter Ravdin, MD, who moderated a press conference at the San Antonio Breast Cancer Symposium at which these data were presented. Ravdin, who was not involved in the study, is the director of the Breast Health Clinic at the Cancer Therapy & Research Center of the University of Texas Health Science Center at San Antonio.
The large, individual patient meta- analysis was based on 36 randomized controlled trials with a total of 22,982 women that compared adjuvant use of bisphosphonate versus no bisphosphonate or placebo. Seven of the trials compared the bisphosphonate clodronate versus no bisphosphonate or placebo and 29 evaluated aminobisphosphonates versus no bisphosphonate or placebo (65% of the women taking aminobisphosphonates received zoledronic acid, 24% iban-
dronate, and 11% “other”).
In the overall trial, no significant difference was observed in the 10-year rate of all breast cancer recurrences or distant recurrences, including bone recurrences.
The effect of bisphosphonates was confined to 11,306 postmenopausal women (including women aged >55 years if menopausal status was unknown); bisphosphonates achieved a highly significant difference compared with no bisphosphonates in distant recurrence (18.4% vs 21.9%, respectively; P = .0003) and in bone recurrence (5.9% and 8.8; P
<.00001). Bisphosphonates did not significantly reduce distant recurrences other than in bone in postmenopausal women.
The rate of breast cancer mortality was 15.2% for postmenopausal women treated with bisphosphonates compared with 18.3% not receiving bisphosphonates (P = .004), and the rate of all-cause mortality was 21.5% versus 23.8%, respectively (P = .007).
Coleman R, Gnant M, Paterson A, et al; Early Breast Cancer Clinical Trials Collaborative Group (EBCTCG)’s Bisphosphonate Working Group. Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: a meta-analysis of individual patient data from randomized trials. Presented at: San Antonio Breast Cancer Symposium; December 12, 2013; San Antonio, TX. Abstract S4-07.
New Standard of Care for Transplant-Ineligible Patients With Myeloma
Continuous treatment with lenalidomide and low-dose dexamethasone (Rd) was superior to standard treatment with melphalan, prednisone, and thalidomide (MPT) for 72 weeks in newly diagnosed patients with multiple myeloma (MM) who were transplant ineligible. Experts said that these results represented a new standard of care for these patients.
Patients treated with Rd were 28% less likely to progress or die compared with those patients who received standard MPT (the primary end point of the trial). Rd was superior to MPT for all secondary end points, including overall survival, response rates, and duration of response. Patients treated with Rd had fewer secondary hematologic malignancies than those patients in the MPT arm.
“Traditionally, newly diagnosed MM patients have received short bursts of treatment, while continuous treatment was reserved for relapsed patients. However, we believe that these new results will help encourage more research on the efficacy and safety of continuous treatment for newly diagnosed patients to help maximize their changes for overall long-term survival,” stated lead author Thierry Facon, MD, Service des Maladies du Sang, Hôpital Claude Huriez, and CHRU Lille, France, at the American Society of Hematology annual meeting.
“For some patients with low-risk MM, this continuous regimen could make this disease a manageable, chronic condition,” he stated.
The multicenter, phase 3 FIRST (Frontline Investigation of Lenalidomide + Dexamethasone Versus Standard Thalidomide) trial enrolled 1623 newly diagnosed patients with MM who were ineligible for stem cell transplant because of older age (>65 years) or other factors such as comorbidities.
Participants were randomized to 1 of 3 arms:
- Continuous Rd in 28-day cycles until disease progression,
- Rd for 18 cycles (72 weeks), or
- 12 cycles of MPT (72 weeks).
Antithrombotic prophylaxis was included in the protocol. Doses of antimyeloma drugs were adjusted for adverse events.
At a median follow-up of 37 months, the primary end point of progression-free survival (PFS) was reached, with a highly significant 28% reduction in risk of disease progression or death for those treated with Rd versus MPT (P = .00006). Median PFS was 25.5 months for continuous Rd compared with 21.2 months for MPT.
Median survival was also significantly better for continuous Rd than for Rd for 18 cycles: 25.5 months versus 20.7 months (P = .00001).
Four-year overall survival was 59% with Rd compared with 51.4% for MPT; 4-year survival in patients receiving Rd for 18 cycles was 55.7%.
Adverse events were similar in both arms, with the exception of less myelosuppression and fewer secondary hematologic malignancies in the Rd arm.
Facon T, Dimopoulos MA, Dispenzieri A, et al. Initial phase 3 results of the First (Frontline Investigation of Lenalidomide + Dexamethasone Versus Standard Thalidomide) trial (MM-020/IFM 07 01) in newly diagnosed multiple myeloma (NDMM) patients (Pts) ineligible for stem cell transplantation (SCT). Presented at: 2013 American Society of Hematology Annual Meeting; December 8, 2013; New Orleans, LA. Abstract 2.
Anastrozole Halves Risk of First Breast Cancer
Treatment with 5 years of anastrozole reduced the risk of developing a first breast cancer by 53% and reduced the risk of developing estrogen-receptor positive (ER+) invasive cancer by 58% in women at high risk for developing the disease. These results from the IBIS-II trial were reported at the San Antonio Breast Cancer Symposium.1
“We believe these results provide strong support for chemoprevention of breast cancer in high-risk women. Longer-term follow-up is needed to determine if the preventive effect is sustained after treatment,” said lead author Jack Cuzick, PhD, Queen Mary University, Wolfson Institute of Preventive Medicine, London, United Kingdom.
IBIS-II randomized 3864 postmenopausal women at high risk of breast cancer, either because of family history and other risk factors (including atypia, lobular carcinoma in situ, or breast density), to treatment with anastrozole or use of placebo for 5 years.
At 7 years of follow-up, primary breast cancers (including ductal carcinoma in situ) developed in 5.6% of women in the placebo group compared with 2.8% of the anastrozole group, representing a 53% decrease (P <.0001). ER+ invasive breast cancers developed in 3.3% of the placebo group versus 1.4% of the anastrozole group, representing a 58% decrease in risk (P = .001). Anastrozole had no protective effect against developing ER-negative tumors.
The full 5 years of the study was completed by 72% of placebo patients and 68% of those taking anastrozole. Cuzick said this 4% difference in treatment continuation suggests that dropouts due to anastrozole-specific adverse effects were quite low.
Anastrozole was associated with bone fractures in 7.7% of placebo patients and 8.5% of those taking anastrozole. Participants had a dual-energy X-ray absorptiometry (DEXA) scan at study initiation, and women with low bone mass were prescribed bisphosphonate treatment, which could account for the smaller-than-expected incidence of musculoskeletal/fracture adverse effects seen in this trial, Cuzick said.
Musculoskeletal aches and pains were 10% higher with anastrozole than in placebo patients. Cuzick said that at baseline, many women in both groups reported joint pain. Other joint symptoms observed more frequently in the anastrozole group were joint stiffness and carpal tunnel syndrome.
Surprisingly, the incidence of other primary cancers was reduced in the group taking anastrozole: 40 patients in the anastrozole group developed other cancers while 70 patients in the placebo group developed other cancers, mainly skin and colorectal cancers. “This merits further study, and the reasons for this effect are unclear,” Cuzick noted.
Study results were published online in the Lancet to coincide with Cuzick’s presentation at the 2013 San Antonio Breast Cancer Symposium.2
- Cuzick J, Sestak I, Forbes JF, et al. Breast cancer prevention using anastrozole in postmenopausal women at high risk. Presented at: San Antonio Breast Cancer Symposium; December 12, 2013; San Antonio, TX. Abstract S3-01.
- Cuzick J, Sestak I, Forbes JF, et al; IBIS-II Investigators. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. December 12, 2013. Epublished ahead of print.
Obinutuzumab Plus Chlorambucil in CLL: New Standard of Care
Results of the German CLL11 randomized, controlled clinical trial promise to change the standard of care for first-line treatment of older, sicker patients with chronic lymphocytic leukemia (CLL). The study showed that obinutuzumab (an anti-CD20 monocolonal antibody) plus chlorambucil (OC) was superior to rituximab plus chlorambucil (RC) with an acceptable safety profile, according to final results of the CLL11 trial, which were presented at the American Society of Hematology (ASH) annual meeting. OC prolonged overall survival and progression-free survival, and also improved complete response rate, and minimal residual disease (MRD)-negative status versus RC.
“These results suggest that obinutuzumab can replace rituximab in combination with chlorambucil as first-line therapy in the specific population studied, ie, older patients with comorbidities,” said Valentin Goede, MD, University Hospital Cologne, Germany.
“These findings are significant and potentially practice changing for this large patient population of older CLL patients with comorbidities.”
Goede noted that OC has less toxicity than RC, which is especially important in this compromised patient population that resembles compromised patients with CLL seen in the real world.
CLL11 randomized 781 patients in a 2:1:2 ratio to 3 arms: OC for 6 cycles; chlorambucil for 6 cycles (control); and RC for 6 cycles. At ASH, Goede presented the first results of the direct comparison between OC and RC (but not vs chlorambucil alone).
More grade >3 infusion reactions were initially seen with OC, mainly occurring with the first infusion: 20% with OC compared with 4% with RC. Once this reaction became evident, prophylaxis is now used and fewer infusion reactions are seen. OC did not increase the risk of infection versus RC, he said.
OC was significantly better than RC in achieving response rates and eradication of disease in blood and bone marrow; overall response rates were 78% versus 65%, respectively. The rate of MRD negativity in bone marrow was 19.5% for OC compared with 2.6% for RC (P <.0001); MRD-negative status in blood was achieved in 37.3% versus 3.3%, respectively (P <.0001).
OC led to a 61% improvement in the likelihood of achieving progression-free survival (the primary end point): median progression-free survival was 26.7 months versus 15.2 months for RC (P <.0001).
Overall survival data are not yet mature but, at present, survival is trending toward OC, Goede said.
Goede V, Fischer K, Busch R, et al. Head-to-head comparison of obinutuzumab (GA101) plus chlorambucil (Clb) versus rituximab plus Clb in patients with chronic lymphocytic leukemia (CLL) and co-existing medical conditions (comorbidities): final stage 2 results of the CLL11 trial. Presented at: 2013 American Society of Hematology Annual Meeting; December 8, 2013; New Orleans, LA. Abstract 6.
ASH List for Choosing Wisely Reduces Unnecessary Waste, Prevents Harm, and Saves Money
Hematologists should not use 5 tests and procedures routinely, according to Choosing Wisely recommendations presented at the 2013 American Society of Hematology (ASH) annual meeting.
In 2009, the Institute of Medicine estimated that $210 billion was wasted on unnecessary healthcare services in the United States across all specialties. “If we could redirect even a fraction of this to real people with real unmet healthcare needs, think of the good that we can do,” said ASH’s Choosing Wisely Task Force Chair Lisa Hicks, MD, of St. Michael’s Hospital and the University of Toronto, Canada.
Following are the 5 tests and procedures that were selected by the Task Force:
- Computed tomography scans. Limit their use in asymptomatic patients following curative-intent treatment for aggressive lymphoma. They do not change outcomes.
- Inferior vena cava filters should not be routinely used in patients with acute venous thromboembolism (VTE).
- Do not transfuse more than the minimum number of red blood cell units necessary to relieve symptoms of anemia or to return a patient to safe hemoglobin range (7 to 8 g/dL in stable noncardiac inpatients).
- Do not test for thrombophilia in adults with VTE occurring in the setting of major transient risk factors such as surgery, trauma, or prolonged immobility.
- Do not administer plasma or prothrombin complex concentrates for nonemergent reversal of vitamin K antagonists (ie, outside the setting of major bleeding, intracranial hemorrhage, or anticipated emergent surgery).
The evidence for these recommendations was analyzed and reviewed over a year-long process by the ASH Task Force with input from the ASH membership.
The list includes only recommendations with strong evidence, and the main guiding principle of the process of making recommendations was to “do no harm.” Other guiding principles were level of evidence, cost, frequency, and scope of practice.
Hicks acknowledged that these 5 recommendations are probably only the tip of the iceberg, but said they represent an important first step in providing top quality care and optimizing outcomes for patients and the healthcare system.
Choosing Wisely is a quality care initiative developed by the American Board of Internal Medicine in collaboration with leading medical societies. It is expected to include more than 250 unnecessary tests and procedures from 30 medical specialty societies.
An article was published online in Blood to coincide with the presentation of the Choosing Wisely list at the ASH meeting. The list can be viewed at www.hematology.org/choosingwisely.
Hicks LK. ASH Choosing Wisely® list. Presented at: 2013 American Society of Hematology Annual Meeting; December 9, 2013; New Orleans, LA.