What’s New in Cancer Research
Advances in Cancer Treatment Presented at the 47th Annual Meeting of the American Society of Clinical Oncology
The theme of the 2011 ASCO Annual Meeting, “Patients. Pathways. Progress.” was borne out in the scientific sessions at McCormick Place in Chicago in both the news that came out of the meeting and in the attitudes and philosophies espoused by this year’s presenters and honorees. It is impossible to summarize all of the new science and clinical updates presented at the Meeting — the largest oncology meeting in the world — but this article highlights a few of the presentations that particularly illuminate the collective theme of the meeting.
Accelerating Progress Against Cancer
To mark the 40th year since the signing of the National Cancer Act of 1971, the opening press briefing of the 47th Annual Meeting of the American Society of Clinical Oncology highlighted the significant progress made in cancer treatment over the past four decades, the major challenges ahead, and new research models to find better treatments faster.
“Over the past four decades, the average five-year survival rate for all cancers has increased by 18 percent, so that today, two out of three cancer patients live at least five years after a cancer diagnosis,” said George W. Sledge Jr., MD, ASCO president and the Ballve-Lantero Professor of Oncology and professor of Pathology and Laboratory Medicine at the Indiana University School of Medicine. “Since its peak in 1991, the overall cancer death rate has dropped by 17 percent. This progress has occurred not by chance, but through many decades of public and private funding of cancer research. Sustained investment in cancer research will continue to offer hope for patients worldwide.”
To demonstrate the progress that has been made in cancer research, ASCO has launched a dynamic new website featuring an interactive timeline of major milestones in cancer research overall in several common cancer types over the past 40 years. The new site, CancerProgress.Net, is designed to be a “living” site where new advances and information will be added in real time.
BRAF Inhibitor Shows Improved
Survival in Advanced Melanoma
A phase III trial has shown that vemurafenib (also known as PLX4032), which targets the V600E mutations in the BRAF gene, is the first targeted drug to improve overall survival when compared to standard chemotherapy in people with advanced melanoma. It is also the first drug to improve progression-free survival and response rate in this group. Approximately half of all melanomas harbor a V600E mutation in the BRAF gene. If approved by the U.S. Food and Drug Administration, vemurafenib could become a new standard treatment for people with melanoma who have this gene mutation.
“This is really a huge step toward personalized care in melanoma,” said lead author Paul Chapman, md, attending physician in the melanoma/sarcoma service at Memorial Sloan-Kettering Cancer Center in New York. “This is the first successful melanoma treatment tailored to patients who carry a specific gene mutation in their tumor, and could eventually become one of only two drugs available that improves overall survival in advanced cancers.” The other drug, ipilimumab, is featured below in our ASCO coverage.
First-Line Ipilimumab Plus Chemotherapy
Improves Overall Survival
in Metastatic Melanoma
A phase III study has found that first-line treatment with a combination of the immunotherapy drug ipilimumab (Yervoy™) and the standard chemotherapy drug dacarbazine improves overall survival in people with previously untreated metastatic melanoma. It is the first study to show that combining chemotherapy and immunotherapy is safe and effective for people with advanced melanoma.
Ipilimumab is a monoclonal antibody that represents a new class of drugs that activate the immune system’s T cells, which then seek and destroy melanoma cells. The drug, which recently received FDA approval for use as a single-drug therapy in advanced melanoma, targets the cytotoxic T-lymphocyte associated antigen 4, which acts like a brake on the T-cell. Ipilimumab removes this brake, enabling T cells to attack the cancer.
New High-Dose Chemotherapy Regimen
Improves Survival in Children with
A phase III trial has shown that children with high-risk neuroblastoma, a common pediatric cancer, had better event-free and overall survival with a combination of the myeloablative chemotherapy drugs busulphan and melphalan compared to a different myeloablative regimen of three chemotherapy drugs: carboplatin, etoposide, and melphalan. These results establish a new standard of care for children with high-risk disease, of whom previously only 30 percent survived long-term. Myeloablative chemotherapy is high-dose chemotherapy that kills cells in the bone marrow, including cancer cells.
“The study’s results are important for patients with this extremely difficult to treat disease,” said lead author Ruth Ladenstein, MD, MBA, associate professor of Pediatrics at the University of Vienna and St. Anna Children’s Cancer Research Institute in Vienna. “These results, combined with the recent report that an anti-GD2 ch14.18 antibody-based immune therapy can increase event-free and overall survival by 20 percent in high-risk patients, mean that we could potentially improve overall prognosis by up to 35 percent in the future.”
New Chemotherapy Regimen Boosts
Event-Free Survival for Children and
Young Adults with Leukemia
A Children’s Oncology Group study has shown that a high-dose methotrexate regimen is superior to the standard regimen of escalating methotrexate for children and young adults with high-risk B-precursor acute lymphoblastic leukemia. This regimen improved five-year event-free survival and had no greater significant side effects compared to the standard regimen. The trial establishes a new standard treatment for this group.
“Pediatric ALL was once a deadly form of leukemia, and now it’s one of the most curable. This trial helps us address an important need for patients with this disease. With these results, we now have an approach that will raise cure rates even higher,” said Eric C. Larsen, MD, principal investigator of the study and director of the Maine Children’s Cancer Program and the Division of Pediatric Hematology/Oncology at the Barbara Bush Children’s Hospital at Maine Medical Center. “Based on the findings from this trial, all current and upcoming treatment protocols for children with newly diagnosed high-risk B-precursor ALL will use this regimen.”
New Lung Cancer Consortium Identifying
Tumor “Driver” Mutations in Advanced
Cancer to Improve Treatment Choice
The ability to detect mutations that drive the development of lung cancer and subsequently target them with specific drugs has changed the management of the disease. In a prospective study, the Lung Cancer Mutation Consortium has identified at least one of ten recognized “driver” mutations in tumors in nearly two-thirds of people with advanced lung cancer. Investigators suggest that the Lung Cancer Mutation Consortium program is an important model for care and research, showing that a person’s tumor may be analyzed for mutations at diagnosis in a systematic way, and data can be given to physicians to help guide care of that person to use available targeted therapies or encourage participation in clinical trials.
“Over the past decade, it’s become clear that adenocarcinoma of the lung – the most common type of lung cancer – is defined by types of DNA damage in the tumor. While identifying the specific mutations can inform treatment decisions and improve outcomes, many centers have not routinely done this because of a lack of funding and available testing technology for mutations,” said lead author Mark G. Kris, MD, chief of the Thoracic Oncology Service and The William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan- Kettering Cancer Center in New York. “The idea behind the consortium was to create a lasting process at each institution to routinely obtain information on tumor mutations and use it to choose the most appropriate therapy for each patient. It’s a proof of concept that individual institutions can do this routinely at diagnosis.”
Extending Pemetrexed Treatment
as Maintenance Therapy Improves
Progression-Free Survival in People
with Advanced Lung Cancer
Results from a recent study show that maintenance therapy with the chemotherapy drug pemetrexed (Alimta®) improves progression-free survival in people with advanced nonsquamous nonsmall cell lung cancer who also received pemetrexed as part of their initial chemotherapy regimen. The study provides physicians with a new treatment option after first-line therapy with pemetrexed.
“Cisplatin-pemetrexed therapy is an effective induction therapy for advanced disease. But after the fourth course, we typically stop treatment, and eventually need to go to a second-line therapy when the disease progresses again,” said lead author Luis Paz-Ares, MD, PhD, chair of Oncology at Seville University Hospital in Seville, Spain. “This cancer doesn’t have many treatment options, and we don’t want to fire all of our treatment bullets at once. These results suggest that patients can still continue to benefit from the use of the same drug rather than ‘use up’ an alternative early in the course of treatment. This could change the standard of care for these patients, at least in terms of maintenance treatment.”
Flaxseed Ineffective in Reducing
A new study has found that flaxseed did not reduce hot flashes in postmenopausal women who reported experiencing at least 28 hot flashes per week. The trial included women with and without a history of breast cancer.
Three Years of Imatinib Therapy
Improves Survival for High-Risk GIST
A new study has shown that three years of treatment with imatinib (Gleevec®) after surgery in people with high-risk gastrointestinal stromal tumors (GIST) improved overall and recurrence-free survival compared to one year of treatment. The findings could result in the three-year course of therapy becoming the new standard of care for people with GIST who are at risk for relapse.
Adding Regional Nodal Irradiation
Decreases Recurrences in Women
with Early Breast Cancer
Interim analysis data from a phase III trial show that in women with nodepositive or high-risk node-negative breast cancer, additional radiation treatment to the regional lymph nodes (regional nodal irradiation) improves disease-free survival, reducing cancer recurrences both near the tumor site and in other parts of the body. In addition, overall mortality was reduced by 24 percent in the group receiving regional nodal irradiation, but this did not reach statistical significance.
“These results are potentially practice-changing. They will encourage physicians to offer all women with node-positive disease the option of receiving regional nodal irradiation,” said Dr. Timothy J. Whelan, BM, BCh, lead study investigator for the NCIC Clinical Trials Group and a professor of Oncology and division head of Radiation Oncology at McMaster University and the Juravinski Cancer Centre, Hamilton, Ontario. “Adding regional nodal irradiation improved disease-free survival, lowered the risk of recurrences, and there was a positive trend toward improved overall survival, while not greatly increasing toxicities.”
Bevacizumab Extends Progression-Free
Survival in Recurrent Ovarian Cancer
The randomized phase III OCEANS study of bevacizumab (Avastin®) in combination with platinum-based chemotherapy showed that women with recurrent ovarian cancer who took bevacizumab lived significantly longer without their disease getting worse. A 52-percent reduction in the risk of disease progression was seen.
“Women taking bevacizumab lived for longer periods without disease progression and without having to go back on chemotherapy,” said Carol Aghajanian, MD, lead study author and chief of the Gynecologic Medical Oncology Service at Memorial Sloan-Kettering Cancer Center in New York. “This is good news for women with these cancers, as we are increasingly able to treat ovarian cancer as a chronic disease.”
Initial Data on Use of Bevacizumab
for Newly Diagnosed Ovarian Cancer
Suggests Survival Benefit for Women
at High Risk of Recurrence
Interim survival data from a phase III trial suggests that adding bevacizumab (Avastin) to standard carboplatin and paclitaxel chemotherapy for treatment of newly diagnosed ovarian cancer may offer benefit over treatment with chemotherapy alone, particularly for women with more aggressive disease.
♦ ♦ ♦ ♦ ♦