New Developments in Cancer Research
Advances in Cancer Treatment Presented at the 48th Annual Meeting of the American Society of Clinical Oncology
The 2012 ASCO Annual Meeting was held in Chicago, Illinois, from June 1 through June 5, 2012. The ASCO Annual Meeting is the platform for the release of thousands of scientific abstracts – highly anticipated research news for many people, including patients, caregivers, and the general public.
Adding Abiraterone to Hormonal
Therapy before Surgery Can Eliminate
Tumor in the Prostate in Some Men
with High-Risk Prostate Cancer
A phase II study has shown that six months of treatment with the targeted drug abiraterone (Zytiga®), in addition to standard hormonal therapy before surgical removal of the prostate, eliminated or nearly eliminated cancer in one-third of men with localized high-risk prostate cancer.
Abiraterone works by blocking production of the male hormone testosterone and related metabolites that often fuel prostate cancer growth. The addition of abiraterone to traditional hormonal therapy, which restricts testosterone production in a different way, further shuts down the body’s ability to produce the hormones that prostate cancer cells need to grow. The clinical benefit of intensive androgen deprivation therapy, either before or after prostatectomy, will need to be validated in prospective, randomized clinical trials, but these data suggest a benefit for some men.
Adding Bevacizumab to Chemotherapy
for Platinum-Resistant Ovarian Cancer
Improves Progression-Free Survival
Adding bevacizumab (Avastin®) to standard chemotherapy doubled progression-free survival in a phase III trial of women with platinum-resistant ovarian cancer.
The study evaluated bevacizumab added to chemotherapy versus chemotherapy alone in women with epithelial ovarian, fallopian tube, or primary peritoneal cancer with disease progression within six months of their last dose of platinum therapy. All participants received one of three standard chemotherapy drugs normally offered in this setting – weekly paclitaxel, topotecan, or liposomal pegylated doxorubicin. These treatments are equally effective in treatment for resistant ovarian cancer, differing only in their toxicities.
After a median follow-up of 13.5 months, 75 percent of the participants who received bevacizumab in addition to chemotherapy had a recurrence, compared to 91 percent who received chemotherapy alone.
Promising Activity for New PD-1
Targeted Immune Therapy
Results from an early-stage study show that treatment with the investigational drug BMS-936558 caused tumor shrinkage in up to a quarter of people with advanced melanoma, kidney, and nonsmall cell lung cancers. This antibody drug targets a key pathway in T-cells called PD-1, which inhibits the body’s immune response to cancer. By blocking this pathway, BMS-936558 may reactivate the immune system to fight tumor cells.
Intermittent Hormonal Therapy Found
to Be Less Effective Than Continuous
Therapy in Certain Men with Advanced
A clinical trial comparing two common therapies for men with hormone-sensitive metastatic prostate cancer has found that intermittent hormonal therapy is less effective than continuous hormonal therapy in men with minimal disease spread. There was a two-year difference in median survival among these men, favoring men who received continuous therapy. Among men with more extensive disease spread, however, the results indicate that intermittent and continuous therapy are comparably effective.
“Some doctors recommend intermittent hormonal therapy to men with metastatic prostate cancer, believing it will reduce their risk of side effects without compromising their outcome, but these findings demonstrate a clear downside to this approach for certain men,” said Maha Hussain, MD, professor of medicine and urology at the University of Michigan Comprehensive Cancer Center and the study’s lead author. “The findings clearly demonstrate that intermittent hormonal therapy is not safe for all patients with metastatic prostate cancer. They will be practice changing for many doctors in the U.S. and abroad who routinely use intermittent therapy.”
Study Suggests New Treatment Option
for Some Lymphomas
Long-term results from a phase III study show that initial combination chemotherapy with bendamustine (Treanda®) and rituximab (Rituxan®) more than doubled progression-free survival, to nearly six years, compared with standard R-CHOP therapy among people with slow-growing lymphoma and mantle cell lymphoma. The bendamustine regimen was also associated with fewer side effects. The findings are expected to change clinical practice.
“This is the first randomized clinical trial to compare bendamustine and rituximab with a standard chemotherapy regimen for these more challenging types of lymphoma, and it clearly shows that the bendamustine-based regimen is more effective and less toxic,” said Mathias J. Rummel, MD, PhD, professor of medicine at the University Hospital Giessen in Germany and lead author of the study. “Just as important, bendamustine-based therapy allowed patients to have a better quality of life while undergoing therapy. These long-term findings should be strong enough to change clinical practice.”
R-CHOP, a standard chemotherapy regimen for many non-Hodgkin lymphomas, includes the targeted therapy rituximab plus the drugs cyclophosphamide (Cytoxan®), doxorubicin (Adriamycin®), vincristine, and prednisone.
For Some Breast Cancers, New Drug
May Be a Treatment Option
A phase III randomized study of the investigational agent trastuzumab emtansine (T-DM1) versus standard therapy using capecitabine (Xeloda®) and lapatinib (Tykerb®) found significant and clinically meaningful improvement in progression-free survival for T-DM1 in women with HER2-positive locally advanced or metastatic breast cancer previously treated with a taxane and trastuzumab. T-DM1 is an experimental antibody-drug conjugate that consists of the antibody trastuzumab (Herceptin®) linked to the cytotoxic drug emtansine (DM1). The drug’s manufacturer, Genentech, stated it will seek approval from the Food and Drug Administration this year for use of T-DN1 in women with metastatic breast cancer.
Combined Chemo-Radiation Extends
Survival in People with Anaplastic
A phase III study has shown that giving combination chemotherapy after standard radiation therapy delayed tumor growth and extended the lives of people with anaplastic oligodendroglial tumors, a form of brain cancer. A sub-analysis of the study showed the survival benefit of combination chemotherapy-radiation treatment may be limited to people whose tumors contained specific deletions of genetic material in chromosomes 1 and 19.
Continuing Bevacizumab with
Second-Line Chemotherapy after
First Progression Extends Survival
for Advanced Colorectal Cancer
Results from a phase III clinical trial show that combination treatment with bevacizumab (Avastin®) and standard chemotherapy in the second-line setting in people with advanced colorectal cancer who have received first-line bevacizumab combination treatment extends overall survival. These findings validate the treatment that many U.S. oncologists already provide, and they will likely alter the standard of care elsewhere.
“These findings confirm what many physicians and researchers have long suspected – that extended bevacizumab treatment provides meaningful benefits for patients with advanced colorectal cancer, without adding significant side effects,” said Dirk Arnold, MD, director of the Hubertus Wald Tumor Center at the University Cancer Center of University Clinic Eppendorf in Hamburg, Germany, and speaker of the German AIO Colorectal Cancer Collaborative Study Group (which initiated the trial). “But the findings also provide an important new insight about the biology of advanced colorectal cancer, showing us that if the disease develops resistance to chemotherapy, it does not necessarily mean that tumors become resistant to anti-angiogenic therapy. By simply switching chemotherapy drugs when the cancer progresses and continuing with bevacizumab, we can make second-line treatment even more powerful. This finding will likely spur research into other cancer types that are sensitive to both bevacizumab and chemotherapy.”
Afatinib Delays Progression of Advanced
Results from a phase III trial show that initial single-agent oral therapy with the targeted drug afatinib prolongs progression-free survival in people with advanced lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR, also known as ErbB1) mutations, compared with standard chemotherapy. Researchers found that afatinib was particularly beneficial – leading to a doubling of progression-free survival – in the majority of people who had one of two common types of EGFR mutations, deletion 19 or L858R. These two mutations together account for approximately 90 percent of all EGFR mutations.
New MEK Inhibitor, Trametinib, Improves
Survival in Advanced Melanoma
Data from a phase III study show that the oral investigational drug trametinib delayed tumor growth and extended survival for people with advanced melanoma who have BRAF mutations, compared with standard chemotherapy. Trametinib inhibits a protein known as MEK – part of the MAP kinase signaling pathway, of which BRAF is also a component.
“This is the first in a new class of targeted drugs that could benefit patients with melanoma who have BRAF mutations. The findings show that targeting the MEK molecular pathway is a viable strategy for treating many people with the disease,” said Caroline Robert, MD, PhD, head of dermatology at the Institute Gustave Roussy in Paris, France. “Trametinib is likely to become another first-line treatment option for patients with advanced melanoma.”
New BRAF Inhibitor Dabrafenib Delays
Disease Progression Better than
Standard Chemotherapy in People
with Advanced Melanoma
A phase III clinical trial found that treatment with the investigational BRAFtargeted drug dabrafenib reduced the risk of disease progression by 70 percent compared to standard dacarbazine chemotherapy in people with previously untreated, advanced melanoma with mutations in the BRAF gene. The investigators also noted that there appeared to be fewer cases of serious skin toxicities associated with dabrafenib treatment, including squamous cell carcinomas, than have been previously reported in other trials evaluating vemurafenib (Zelboraf®), the current standard targeted drug for this population.
“For three decades, we had no new therapies for metastatic melanoma, but we’re quickly gaining momentum. Last year, ipilimumab and vemurafenib were approved, and now dabrafenib could be on the horizon,” explained lead author and global principal investigator Axel Hauschild, MD, professor of dermatology at the University Hospital in Kiel, Germany.
Newer, More Costly Drugs No Better
than Standard Weekly Paclitaxel as
First-Line Therapy for Locally Advanced
or Metastatic Breast Cancer
A phase III randomized trial found that weekly administration of either of two newer and significantly more costly agents, nanoparticle albumin bound (“nab”) paclitaxel (Abraxane®) and ixabepilone (Ixempra®), was not superior to standard weekly dosing of paclitaxel as first-line therapy for locally advanced or metastatic breast cancer. Furthermore, paclitaxel appears to offer better progression-free survival than ixabepilone and fewer toxicities than nab-paclitaxel in this setting. In practical terms, the findings suggest that many women could do equally well on weekly paclitaxel with fewer side effects and at lower cost.
Duloxetine Is Effective in Treating
A phase III study found that duloxetine (Cymbalta®) is effective in treating painful chemotherapy-induced peripheral neuropathy. Duloxetine is currently approved for the treatment of depression and painful diabetic peripheral neuropathy. Painful peripheral neuropathy – numbness and tingling in the hands and feet – affects 20 to 30 percent of people with cancer treated with taxanes and platinumbased chemotherapy.
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