The much-anticipated findings from two phase III clinical trials of new therapies for patients with metastatic melanoma did not disappoint those in attendance at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago last week.
The trials confirmed that the molecularly targeted agent vemurafenib and the immunotherapy agent ipilimumab (Yervoy) offer valuable new options for a disease in which effective treatments have been lacking. Read more > >
New Substances Added to HHS Report on Carcinogens
Last Friday, the Department of Health and Human Services added eight substances to its Report on Carcinogens, a science-based document that identifies chemicals and biological agents that may put people at increased risk for cancer. Formaldehyde and aristolochic acids are listed as known human carcinogens, and six other substances were added as reasonably anticipated to be human carcinogens.
For more information, read the NIEHS press release.
- FDA Announces Changes to Sunscreen Labels
- No Link Found between Hypertension Drugs and Cancer
- Thermography Is No Substitute for Mammography, FDA Warns
- NCI Director Announces New Staff Appointments
- Abstracts Sought for Annual Molecular Markers in Cancer Meeting
- Research to Reality Cyber-Seminar Will Feature Community Impact Program
- NCI Cancer Classroom Webinar Series Continues June 28
Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.
The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.
For more information about cancer, call 1-800-4-CANCER or visit http://www.cancer.gov.
NCI Cancer Bulletin staff can be reached at email@example.com.
New Therapies Offer Much-Needed Options for Patients with Melanoma
The much-anticipated findings from two phase III clinical trials of new therapies for patients with metastatic melanoma did not disappoint those in attendance at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago last week.
The trials confirmed that the molecularly targeted agent vemurafenib and the immunotherapy agent ipilimumab (Yervoy) offer valuable new options for a disease in which effective treatments have been lacking.
Promising data on melanoma were also seen in a small clinical trial that identified a potential approach to preventing a key side effect of agents with the same molecular target as vemurafenib, a mutated form of the BRAF gene. (See the box at the bottom of the page.) And other lab-based studies identified potential biomarkers that may predict which tumors are more likely to respond to vemurafenib and ipilimumab.
After decades of almost no progress, this new research represents a welcome and long-awaited change, remarked Dr. Lynn Schuchter leader of the melanoma program at the University of Pennsylvania Abramson Cancer Center.
"I think it's a time for celebration for our patients," she said, "for hope."
Vemurafenib: Early Phase III Results Again Show Strong, Rapid Responses
The vemurafenib trial, called BRIM3, enrolled 675 patients with newly diagnosed, inoperable metastatic melanoma, all of whom had tumors with the BRAF mutation. The patients were randomly assigned to receive either vemurafenib or the chemotherapy drug dacarbazine, the standard treatment for most patients with advanced disease. At the first planned interim analysis of trial data at 3 months, there were already statistically significant reductions in the risk of death (63 percent) and disease progression (74 percent) in patients being treated with vemurafenib compared with patients receiving dacarbazine.
Almost half of the patients taking vemurafenib had substantial tumor regressions, compared with fewer than 6 percent of the patients being treated with dacarbazine. Because of the dramatic effect on tumors, patients receiving dacarbazine were switched to vemurafenib, which may complicate the trial's overall survival analysis, several researchers noted.
At the time of the first interim analysis, "we had just finished accrual to the trial," explained the trial's lead investigator, Dr. Paul Chapman of Memorial Sloan-Kettering Cancer Center. "So this is unprecedented to report a trial this early…and yet [the survival] curves separated very early."
However, the trial hasn't gone on long enough to calculate a median overall survival, he noted.
The tumor response rate, although strong, was substantially less than what had been seen in the phase I and II trials of vemurafenib. Even though patients who respond to the treatment typically do so within 2 months of beginning treatment, that is not always the case, Dr. Chapman noted. And given the short follow up, he believes the response rate "will creep up."
The results also confirm that most tumor responses peak after approximately 6 months and that the disease will return. So a priority will be identifying therapies that can help overcome tumor resistance, he said.
Serious toxicities occurred in fewer than 10 percent of patients on vemurafenib, and common side effects of the drug included joint pain; sun sensitivity; and forms of nonmelanoma skin cancer, primarily squamous cell carcinoma (SCC), which occurred in 18 percent of patients. SCC lesions can easily be excised by dermatologists, Dr. Chapman explained, and there have been no cases of metastatic SCC in any of the vemurafenib trials.
Nevertheless, nearly 40 percent of patients taking vemurafenib in the phase III trial had to stop treatment temporarily or have their dose reduced because of side effects.
Ipilimumab: A Subset of Patients Have Prolonged Responses
Results from the ipilimumab trial were far more mature than those from the vemurafenib trial. Five hundred and two patients with metastatic melanoma were randomly assigned to receive the immunotherapy in combination with dacarbazine or dacarbazine alone. Median overall survival improved by just 2 months: 11.2 months versus 9.1 months.
But those figures don't tell the whole story, said the trial's lead investigator, Dr. Jedd Wolchok, also of Memorial Sloan-Kettering Cancer Center. He pointed to the 1-, 2-, and 3-year survival rates, which were all superior in patients who received ipilimumab. At 3 years, approximately 21 percent of patients were still alive in the ipilimumab arm compared with 12 percent in the chemotherapy-only arm.
There was also a 24 percent improvement in progression-free survival in the ipilimumab group, but no statistically significant difference in tumor shrinkage was found between the groups. The length of time for which patients maintained a tumor response was 19.3 months in the ipilimumab arm and 8.1 months in the dacarbazine arm. The greater response duration and survival at 3 years is "consistent with an immunotherapy," Dr. Wolchok said, because immunotherapies are more likely to keep tumors in check rather than produce significant tumor shrinkage.
High-grade adverse events occurred in nearly twice as many patients in the ipilimumab arm (56 percent) as the dacarbazine alone arm (27 percent). Although fewer patients receiving ipilimumab had high-grade diarrhea and colitis (swelling of the large intestine) than in previous trials, Dr. Wolchok explained, liver toxicity was substantially more frequent than previously seen, which he said was likely due to the combination with dacarbazine.
Which Treatment When?
Until the Food and Drug Administration (FDA) approved ipilimumab in March, there were essentially two options for treating advanced melanoma: dacarbazine, which in most patients produces at most modest improvements in survival or symptomatic benefit, and interleukin-2, a highly toxic therapy that induces long-term remissions in only a small percentage of patients.
Roche and Plexxikon, the companies that co-developed vemurafenib, submitted an application for approval to the FDA last month and are expecting a decision some time this year. So, although both ipilimumab and vemurafenib will be options for patients with metastatic disease, a key clinical question remains: Which therapy should be used first in patients whose tumors have a BRAF mutation?
During the meeting's plenary session, Dr. Kim A. Margolin of the University of Washington laid out a potential pattern of use for these patients. "Vemurafenib is appropriate for patients who have symptoms and need to respond fast," she said. "For those with limited tumor burden, limited symptoms, and whose long-term goal is durable benefit and who are not in urgent need of the physical and emotional relief associated with quick tumor regression, ipilimumab may well be the preferred choice."
Because of the serious liver side effects attributed to dacarbazine in the trial, however, she advised that ipilimumab be used alone.
Dr. Schuchter was quick to respond with how she will handle such patients. "I'll put them on a trial," she said. With studies rapidly identifying mechanisms of tumor resistance and potentially effective combinations of therapies, she continued, "we can further characterize patient tumors" by their different genetic abnormalities "and direct them to [trials testing] the right targeted therapies."
A clinical trial "is clearly the top priority," agreed Dr. Sekwon Jang, a medical oncologist at Washington Hospital Center who primarily treats melanoma patients. "We're going to have many more clinical trial options for patients," he said.
On the day before the ASCO meeting began, in fact, Roche and Bristol-Myers Squibb, the manufacturers of vemurafenib and ipilimumab, announced that they had entered into a collaborative agreement to conduct clinical trials testing the agents in combination.
If a patient cannot be enrolled in a clinical trial for some reason, Dr. Schuchter said, vemurafenib would likely be her first-line therapy of choice for most patients with BRAF mutations.
During an education session on melanoma therapy, Dr. Antoni Ribas of UCLA's Jonsson Comprehensive Cancer Center, who has been involved in studies of both agents, said he hoped that ipilimumab's less robust response rate compared with that of vemurafenib will not deter oncologists from using it. "It's unquestionable that ipilimumab has a positive impact on overall survival," he said.
Based on the clinical trial data, he continued, it's clear that a modest proportion of patients will have long, objective responses "and are probably cured."
Cancer Research Highlights
Ovarian Cancer Screening Method Fails to Reduce Deaths from the Disease
New results from the NCI-sponsored Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial show that screening for ovarian cancer with transvaginal ultrasound (TVU) and the CA-125 blood test did not result in fewer deaths from the disease compared with usual care. In addition, false-positive results from the two screening methods often led to unnecessary surgeries and other serious complications. The results were presented June 4 at the American Society of Clinical Oncology (ASCO) annual meeting and appeared online June 8 in JAMA.
The PLCO trial is a randomized, controlled trial of adults 55 to 74 years of age. The 78,216 women who enrolled were assigned to undergo either annual screening with TVU and CA-125 testing or to receive usual care. (Most women in the usual care group underwent bimanual examination with ovarian palpation.) Participants were screened at 10 centers across the United States between November 1993 and July 2001 and were followed for up to 13 years. There were 118 deaths from ovarian cancer in the screened group compared with 100 deaths in the usual-care cohort.
The false-positive rate in the PLCO trial was approximately 5 percent of those screened during each round of screening. Of the 3,285 women with false-positive results in the study, 1,080 underwent surgical follow-up. Among those, 163 women (15 percent) experienced at least one serious complication. A 2009 report on the PLCO study found that many of the positive screening results from TVU and CA-125 turned out not to be cancer. The researchers estimated that only 1.6 out of every 100 women who test positive for signs of ovarian cancer with these tests actually have cancer.
With these results, and the efficacy of these tests being ruled out, investigators will explore other screening options, the study authors noted. Some evidence suggests that ovarian tumors need to be found when they are relatively small—considerably smaller than the current threshold used for TVU, explained Dr. Christine Berg of NCI’s Division of Cancer Prevention. “Had the trial tested a lower CA-125 threshold, it may have been possible to detect cancers at an earlier stage,” said Dr. Berg. “However, this would be at the expense of more false-positive results and perhaps overdiagnosis of benign tumors.”
Longer Imatinib Treatment for GIST Improves Survival
Prolonging treatment of patients with high-risk gastrointestinal stromal tumors (GIST) with the tyrosine kinase inhibitor imatinib (Gleevec) after surgery improved overall and recurrence-free survival in a prospective randomized multicenter trial. The trial results were presented June 5 at the ASCO annual meeting by lead author Dr. Heikki Joensuu of Helsinki University Central Hospital, Finland.
Researchers randomly assigned 400 patients with operable GIST who were at high risk for recurrence to either 1 or 3 years of adjuvant imatinib therapy. After a median follow-up of 54 months, the investigators found that 5-year recurrence-free survival was higher in the 3-year treatment group (65.6 percent) than in the 1-year treatment group (47.9 percent). Similarly, 5-year overall survival for patients in the 3-year treatment group (92.0 percent) was higher compared with that of patients who received adjuvant imatinib for only 1 year (81.7 percent).
“What really pleases me about this study is the impact on overall survival,” Dr. Joensuu said at an ASCO press briefing. Based on historical data before the introduction of imatinib treatment of high-risk GIST, “perhaps 50 percent of these patients would have died within the first 5 years, and now we are looking at 92 percent overall survival among the 3-year treatment group, which is very high,” he noted. In addition, there was a 55 percent reduction in the risk of death in the 3-year treatment group compared with the 1-year group, “a substantial reduction which is also statistically significant,” he said.
The researchers found that the longer imatinib regimen was generally well tolerated, and few of the patients developed resistance to the drug, which is in line with previous studies. Only 2 percent and 6.1 percent of patients in the 1- and 3-year groups, respectively, stopped treatment because the disease recurred.
“This might be the first example of long-term adjuvant therapy with a targeted small-molecule tyrosine kinase inhibitor, and it’s likely to become standard treatment,” said Dr. Joensuu in a press release.
High-Dose Methotrexate Extends Event-Free Survival for Children with Leukemia
Children’s Oncology Group researchers have shown in a phase III clinical trial that radically increasing the dose of methotrexate used to treat patients with high-risk B-cell acute lymphoblastic leukemia (B-cell ALL) significantly improves 5-year event-free survival (that is, survival without any serious health events) when compared with the current standard of care. The trial results were presented last week at the ASCO annual meeting.
In the current standard of care, known as the Capizzi regimen, patients are started on a low dose of methotrexate, and the dose is increased gradually over time. Methotrexate is then followed by treatment with a second chemotherapy drug called asparaginase. In the new approach, however, patients are given a dose of methotrexate that is about 50 times the starting dose in the Capizzi regimen, and asparaginase is not used.
The next generation of clinical trials involving patients with high-risk B-cell ALL will use the high-dose methotrexate regimen, said the trial’s lead investigator, Dr. Eric Larsen of Maine Medical Center. “Even for children not on a trial, it’s likely that this approach will be adopted.”
The Capizzi regimen has been very effective, improving cure rates for ALL by reducing relapses in the bone marrow, where the disease initially occurs. The investigators hypothesized that a high-dose regimen of methotrexate would more effectively target cancer cells in the central nervous system (CNS), where most B-cell ALL relapses occur.
The trial began in 2004 but was closed early in January 2011, Dr. Larsen explained, when a planned interim analysis showed that the high-dose methotrexate approach led to “clearly superior” 5-year event-free survival: 82 percent versus 75 percent. The high-dose methotrexate group also had significantly fewer bone-marrow and CNS tumor relapses.
Patients in the trial treated with the Capizzi regimen who were not more than a year into their treatment were given the choice of switching to the high-dose regimen, Dr. Larsen noted. Most, but not all, chose to switch.
“We were concerned that the high-dose methotrexate regimen would be more toxic, but it was found to be less toxic than the Capizzi regimen,” Dr. Larsen said.
The higher incidence of side effects in patients treated with the Capizzi regimen may be due to the asparaginase, Dr. Larsen suggested. Also, another chemotherapy drug, leucovorin, is typically used as a “rescue” therapy to help prevent common side effects associated with high doses of methotrexate (such as low blood cell counts, mouth sores, and diarrhea), which also likely helped explain the differences in toxicity of the two regimens, explained Dr. Lisa Diller of the Dana-Farber Cancer Institute and a Children’s Oncology Group investigator.
The high-dose methotrexate regimen should become the new standard of care in high-risk B-cell ALL, Dr. Diller agreed. Even with the gains in survival seen in pediatric cancer, she continued, the results are further evidence that with well-designed clinical trials “we can find new ways to improve outcomes with old drugs.”
Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients
Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival. Longer follow-up is needed to confirm the trends, but, if upheld, the results of these trials would support the first use of a biologic agent to treat ovarian cancer. Data from both trials were presented last week at the ASCO annual meeting in Chicago.
In the OCEANS study, 484 women whose cancers recurred more than 6 months after a single prior regimen of chemotherapy were randomly assigned to receive chemotherapy with carboplatin and gemcitabine plus bevacizumab or a placebo. After six cycles of chemotherapy, the patients continued to receive bevacizumab or the placebo until evidence of tumor progression was seen. Those who received bevacizumab had a 52 percent increase in the time it took their disease to progress compared with those who received placebo (12.4 months versus 8.4 months, respectively).
Tumor shrinkage was observed in 79 percent of the patients treated with bevacizumab, compared with only 57 percent of those receiving the placebo. The duration of tumor response was also longer in patients receiving bevacizumab by an average of 3 months. Side effects were similar to those seen in other studies of bevacizumab, such as increased hypertension and proteinuria. No gastrointestinal perforations were reported.
“This regimen should be considered a new option for women with recurrent ovarian cancer [whose cancer responded to plantinum-based chemotherapy],” said the study’s lead investigator Dr. Carol Aghajanian of Memorial Sloan-Kettering Cancer Center.
In the second trial, known as ICON7, 1,528 women with newly diagnosed high-risk or advanced ovarian cancer were randomly assigned to six cycles of chemotherapy with carboplatin and paclitaxel alone or to six cycles of chemotherapy with bevacizumab, followed by bevacizumab alone for 12 cycles. The addition of bevacizumab modestly increased the time it took patients’ tumors to grow, from 17.4 months to 19.8 months. An interim analysis of overall survival showed fewer deaths among patients who received bevacizumab, but this difference was not statistically significant.
The subgroup of patients at the highest risk of recurrence—patients with stage IV disease or those with stage III disease who had more than 1 cm in diameter of remaining tumor after debulking surgery—had a statistically significant improvement in overall survival, 36.6 months versus 28.8 months, and a 36 percent reduction in the risk of death.
Longer follow-up is needed to more definitively determine whether there is an overall survival benefit for high-risk patients, acknowledged the study’s lead investigator, Dr. Gunnar Kristensen of the Norwegian Radium Hospital in Oslo. But, he continued, the current data suggest that, for these patients, bevacizumab “may be of clinical relevance.”
The results from the OCEANS and ICON7 trials—and results from a trial reported at last year’s ASCO meeting, GOG 218, which showed a nearly 4-month improvement in progression-free survival for women who received chemotherapy and bevacizumab as initial therapy for advanced ovarian cancer—are not yet enough to support using bevacizumab to treat ovarian cancer, said Dr. Ursula Matulonis of the Dana-Farber Cancer Institute.
The findings to date, she continued, “are certainly very exciting.” But given the potential serious side effects of bevacizumab, particularly bowel perforation, it’s important to proceed with caution. “Ideally, we would have a biomarker that would predict responsiveness to bevacizumab,” Dr. Matulonis said, “one that identifies an angiogeneic subtype that you could use to select patients who would benefit most.”
Experimental Drug Shrinks Tumors in Rare Sarcoma
In a phase II clinical trial of the experimental drug cediranib, more than half of patients with a rare type of cancer called alveolar soft part sarcoma (ASPS) saw their tumors shrink. Results from 33 patients participating in the study were presented at the ASCO annual meeting in Chicago on June 6.
ASPS is a form of soft tissue sarcoma that strikes teens and young adults. It usually develops in the muscle or other soft tissue of the arms, legs, pelvic region, or head and neck area. Because ASPS tumors typically cause no pain and grow slowly, they are often not discovered until the cancer has reached an advanced stage. There is currently no accepted standard of care for patients with advanced ASPS.
Cediranib interferes with several proteins that help tumors develop the new blood vessels they need for continued growth and spread throughout the body, a process known as tumor angiogenesis. NCI’s Division of Cancer Treatment and Diagnosis (DCTD) and Center for Cancer Research launched the study at the NIH Clinical Center based on the observation that ASPS tumors are highly dependent on angiogenesis, as well as on early findings from a British clinical trial of cediranib involving patients with different types of tumors, including some with ASPS. The research team was led by Dr. Shivaani Kummar of DCTD.
In the ongoing trial, patients take cediranib by mouth daily until their disease progresses or intolerable side effects develop. In the subset of data from 33 patients presented at ASCO, side effects included high blood pressure and diarrhea, both of which were manageable. Some of these patients were still taking cediranib after more than a year of treatment.
“It is unusual to see such high levels of tumor shrinkage in a cancer that traditionally has not responded to standard chemotherapy used for the treatment of sarcomas,” said Dr. Kummar. “These are exciting results that warrant further evaluation.”
International Study Tests Additional Radiation Therapy for Breast Cancer
Positive preliminary results from an international clinical trial evaluating the use of additional radiation therapy for early-stage breast cancer were presented at the ASCO annual meeting last week. The risk of cancer recurrence was lower among women in the study who received additional radiation to nearby lymph nodes than among women who did not, according to interim results from the trial.
The National Cancer Institute of Canada led the randomized phase III study, called MA.20, with participation from NCI’s Clinical Trials Cooperative Group Program. Most of the patients enrolled had early-stage disease that had spread to nearby lymph nodes (node-positive) or were at high risk of a recurrence based on the size of their primary tumors. The vast majority of the patients were node-positive, meaning they had one to three lymph nodes with evidence of cancer, Dr. Timothy Whelan of McMaster University in Ontario explained in his presentation. All patients had breast-conserving surgery followed by chemotherapy or endocrine therapy.
Overall, after a median follow-up of more than 5 years, the women who received whole-breast irradiation as well as additional radiation to the nearby or regional lymph nodes, called regional nodal irradiation (RNI), had a statistically significant improvement in disease-free survival compared with the women who had received whole-breast irradiation without RNI.
The study’s primary endpoint was overall survival. The interim results showed an overall survival improvement among the RNI group compared with the non-RNI group, but the improvement was not statistically significant. (The 5-year overall survival rates were 92.3 percent versus 90.7 percent, respectively.) Whether this will change as the study continues remains to be seen.
Based on the findings, Dr. Whelan recommended that women with one to three positive nodes should be offered RNI, “provided that they are made aware of the associated toxicities.”
During a discussion of the results at the meeting, Dr. Thomas Buchholz of the University of Texas M. D. Anderson Cancer Center noted that the group of women who could be considered candidates for this treatment is heterogeneous. Not all patients with one to three positive lymph nodes “have the same risk of residual regional disease and, therefore, would not [all] receive the same benefit from this procedure,” he explained.
Dr. Buchholz also said that additional data were needed before he would consider offering the treatment to certain patients, including those who may have more favorable prognoses. Biological markers for identifying and distinguishing these subgroups are needed, he added.
Patient Navigation Leads to Fewer Missed Oncology Appointments
An analysis of patients at a large Chicago-area hospital found that using a patient navigation service dramatically improved patient compliance with appointments for cancer radiation therapy. Results of the study at John H. Stroger Hospital of Cook County, which serves an urban, largely medically underserved population, were presented in a poster session at the ASCO annual meeting on June 4.
Researchers compared patients who were provided access to a patient navigation service (case patients) with those who were patients prior to the institution of such a program (control patients). Patients were matched on the basis of tumor site, disease stage, race, sex, and age. In addition to comparing case and control patients, the researchers also examined appointment compliance among case patients before and after the patients began using the navigation service. The service helped patients obtain assistance for transportation, child care, insurance, housing, education, and support for emotional needs.
The results showed that case patients with breast cancer were more likely to keep their appointments after receiving navigation assistance, with missed appointments dropping from 18 percent before assistance to 3 percent afterward. The number of patients with any cancer who kept all appointments rose from 24 percent before navigation assistance was offered to 36 percent, whereas the proportion of patients not completing their scheduled course of radiation therapy for nonmedical reasons fell from 19 percent to 6 percent.
Missed appointments can delay or compromise treatment, potentially leading to poorer outcomes, explained the study’s lead investigator, Dr. Elizabeth Marcus, adding that regardless of insurance status, one of the most common reasons for missed appointments was a lack of transportation. “It was often just an inability to get there,” she said.
In addition to demonstrating the value of patient navigation services, Dr. Marcus said the study showed that “having insurance doesn’t necessarily mean patients always have access to care.” She explained that trial participants will continue to be followed to determine whether improved appointment compliance improves survival, as well as to analyze the cost effectiveness of the navigation services.
The Illinois division of the American Cancer Society funded the study.
Exemestane Substantially Reduces Breast Cancer Risk
The list of drugs that have been shown to reduce a woman's chance of developing breast cancer can now be expanded from two to three. Clinical trial results presented at the American Society of Clinical Oncology's (ASCO) annual meeting last week showed that the aromatase inhibitor exemestane (Aromasin)—commonly used to treat early and advanced-stage breast cancer—substantially reduced the risk of invasive breast cancer in postmenopausal women at high risk of developing the disease.
The findings were also published online June 4 in the New England Journal of Medicine (NEJM).
At 3 years of follow-up, women who took exemestane were 65 percent less likely than women who took a placebo to develop breast cancer. This is the largest reduction in risk seen in any of the four large breast cancer prevention trials that have been conducted to date. In previous trials, daily use of tamoxifen or raloxifene reduced breast cancer risk by approximately 50 percent and 38 percent, respectively, after 5 years of follow-up; both drugs were eventually approved by the Food and Drug Administration (FDA) to reduce breast cancer risk.
Some researchers cautioned that 3 years of follow-up may not be long enough to determine the extent of any serious side effects, including osteoporosis, from long-term use of aromatase inhibitors in this patient population.
—Dr. Paul Goss
Despite the limited follow-up, the trial's principal investigator, Dr. Paul Goss of Harvard Medical School, said the findings were enough to establish exemestane "as a new option for breast cancer prevention in postmenopausal women." All women older than 60, who by virtue of their age alone have an increased breast cancer risk, "should be made aware of these results," he continued.
Sponsored by the National Cancer Institute of Canada, the trial, dubbed MAP.3, enrolled 4,560 women at increased risk of developing breast cancer. A high-risk determination was made based on at least one of several risk factors: age of 60 years or older; a history of abnormal breast cell growth or having had a noninvasive lesion known as ductal carcinoma in situ (DCIS); or an elevated 5-year score on the Gail model, a commonly used breast cancer risk model.
Participants were randomly assigned to take exemestane or a placebo daily for 5 years. Overall, 11 women assigned to exemestane developed an invasive breast cancer compared with 32 women who took the placebo. Exemestane use also led to statistically significant reductions in the development of DCIS, Dr. Goss said, and the invasive tumors that did develop in women taking exemestane were less aggressive than those in the placebo group.
Understanding the Side Effects
Importantly, Dr. Goss stressed, women taking exemestane had no increased risk of serious side effects. "We looked for serious toxicities, but we did not find them," he said. The incidence of osteoporosis, cardiac events, and bone fractures were identical for women taking exemestane and for those taking the placebo. However, women who took exemestane had a small, but not statistically significant increase in menopausal symptoms, such as hot flashes and joint pain.
Overall, approximately 30 percent of participants stopped taking exemestane because of side effects, about 10 percent each year. This is similar to what is seen in clinical practice in women taking an aromatase inhibitor as an adjuvant treatment for early-stage breast cancer.
The data from the MAP.3 trial indicate that exemestane provides another option for risk reduction in the appropriate women, said Dr. Worta McCaskill-Stevens of NCI's Division of Cancer Prevention (DCP). "But when thinking about prevention women ask [about] the duration of use of the drug and [want] a clear understanding of its potential side effects," she cautioned.
Of particular concern is severe joint pain, or arthralgia, whose incidence has been relatively high in women being treated for cancer with aromatase inhibitors.
Several studies, however, have shown that women continued to experience the benefits of treatment after stopping aromatase inhibitors—a phenomenon known as a carry-over effect—and that they have fewer adverse events. The women who participated in MAP.3 will have to be followed to better assess the extent and significance of long-term side effects, especially osteoporosis, she stressed.
Overall, because of the short follow-up in the trial, it's too early to definitively understand the drug's risks, Dr. McCaskill-Stevens added. "We can't say that the adverse events in this group of women will be the same as those seen in women receiving an aromatase inhibitor for treatment," she continued. "That's a different patient population as it relates to assessing benefit and risk."
Dr. Victor Vogel, director of the cancer institute at Geisinger Health System in Danville, PA, who was involved in the tamoxifen and raloxifene prevention trials, called the risk reduction findings with exemestane "very impressive." Many of exemestane's side effects can be prevented and treated with monitoring, he explained.
—Dr. Paul Goss
Even if a woman stops taking exemestane for risk reduction because of side effects, Dr. Goss believes, the effort will have been worthwhile. "We feel comfortable that if a woman takes [exemestane] for 6 months or a year, she's gained benefit," he said.
Several clinical trials currently under way should provide more information about the safety and possible side effects of aromatase inhibitors when used for breast cancer risk reduction, explained Dr. Leslie Ford of DCP.
The British IBIS-2 trial is comparing the aromatase inhibitor anastrazole with a placebo in women at high risk of breast cancer. And a U.S. trial being led by the National Surgical Adjuvant Breast and Bowel Project is comparing the aromatase inhibitor letrozole with tamoxifen in postmenopausal women with DCIS.
More Choices in the Clinic
The failure of tamoxifen and raloxifene to break through into the clinic has been well documented, with women and their doctors citing toxicity as one of their chief concerns. "The good news is that exemestane has a completely different toxicity profile," said Dr. Susan Domchek, director of the Cancer Risk Evaluation Program at the University of Pennsylvania Abramson Cancer Center, who was a site investigator on the trial. "For some women, exemestane will be viewed as a nice choice because of that difference."
As Dr. Vogel stressed, it's not medical oncologists but primary care physicians who would talk with women about their breast cancer risk and whether they should consider taking a drug for prevention. This group of clinicians, along with women themselves, needs to be educated about breast cancer prevention, he explained.
"We need to train primary care physicians about how to do risk assessment; how to counsel these patients," said Dr. Vogel. "And we need to ensure that reimbursement is available so that doctors get paid for taking the time to counsel their patients about preventive interventions."
Several research groups are developing tools to help clinicians with some of the risk assessment and counseling issues, Dr. Domchek noted. In an accompanying editorial in NEJM, Drs. Nancy Davidson and Thomas Kensler of the University of Pittsburgh Cancer Institute noted the need to better identify "high-risk cohorts and biomarkers that can predict response to a particular intervention."
Indeed, as Dr. Andrew Seidman of Memorial Sloan-Kettering Cancer Center noted, unlike with blood pressure or cholesterol medicines, one cannot measure whether tamoxifen, raloxifene, or exemestane is having its intended preventive effect. "There's no feedback loop," he said, to let doctors and women know whether the drug is having the intended effect.
The patent for exemestane expired in 2010, and Pfizer, which manufactures the drug, has not said whether it will apply to the FDA to market exemestane for breast cancer risk reduction.
A Closer Look
Perfect Match: Unraveling the Origin of XMRV
Dr. Vinay Pathak was tying up loose ends at his NCI-Frederick lab and packing for a trip abroad last December, when he received an e-mail message that began, "GOT IT."
The message, from Dr. John Coffin of Tufts University, described a genetic analysis of two mouse viruses. Both viruses—one discovered by Dr. Coffin's lab and the other by Dr. Pathak's—resembled parts of the retrovirus XMRV, but they had never been compared.
When the viral DNA sequences were lined up for the first time, Dr. Coffin wrote in the e-mail, they were nearly a "perfect match" with XMRV (xenotropic murine leukemia virus-related virus). "How the DNA sequences fit together was really remarkable," he said recently. "They clicked like two magnets pulling themselves together."
This single experiment tied together months of clues the researchers had been gathering on the origins of XMRV, which was discovered in prostate cancer cells in 2006. Based on their evidence, Drs. Coffin and Pathak now believed that XMRV arose when the two mouse viruses came together (a process known as recombination) during a lab experiment in the 1990s.
In the experiment, a lab worker was growing a patient's prostate tumor cells in mice until the tumor cells could be cultured—the first step in making a colony of cells, or cell line, for research. When one of the samples was eventually harvested from a mouse, the researchers said, the sample contained XMRV. Then, as many labs began to use the cell line, the virus spread.
The details of this detective story were published online in Science on June 2. In the article, the authors concluded that XMRV emerged when the two "parent" viruses recombined in a lab mouse that was being used to grow human tumor samples.
"These results really tell us that XMRV, as we know it, has not been circulating in the human population," said Dr. Hung Fan, a retrovirologist at the University of California, Irvine, who was not involved in the research.
You must have flash installed and enabled to view the video.
Evidence Points to Contamination
Three years after XMRV was discovered in prostate cancer cells, another group reported finding the virus in patients with chronic fatigue syndrome (CFS). Few labs have been able to confirm this initial report by detecting the virus in patient samples, however, and the possible role of XMRV in human disease has been a source of controversy.
All XMRV isolates reported to date are closely related to the viral sequence found in the prostate cancer cell line known as 22Rv1. If the retrovirus had been replicating in humans, these sequences would contain much more variation, several researchers noted.
Furthermore, the chance of the virus arising independently in another mouse or in the wild is "vanishingly small—about one in a trillion," said Dr. Pathak. This virus is unlikely to exist in nature, so the chance that a person would be exposed to a mouse with the virus is also unlikely, he added.
"Admittedly, we have no direct evidence of a patient sample being contaminated," said Dr. Jonathan Stoye of the United Kingdom's National Institute for Medical Research, who was not involved in the research. "But all of the indirect evidence leads one to believe that contamination is the most likely explanation" for reports of XMRV, he continued.
At a recent workshop on XMRV, co-led by Dr. Stoye, some presenters cautioned that contamination could be a reason that some investigators had detected XMRV in patient samples.
"The [current] study documents a new example of the transfer of viruses from mouse to human cells," said Dr. Stephen Goff, a retrovirologist at Columbia University who also had no role in the study. "This kind of transfer has occurred many times before in other experiments.
"When human tumors are grown in mice," he continued, "the tumors can pick up mouse viruses."
For researchers in the field, a take-home message of the current study is that "anyone who publishes a study saying that XMRV is present in a patient sample needs to look very hard at the data," said the first author, Dr. Tobias Paprotka, a member of Dr. Pathak's lab.
"If it's XMRV, it is almost certainly contamination," added Dr. Pathak.
Testing Prostate Cancer Cells from the Donor
When his investigation began, Dr. Pathak was focused on one question: How had XMRV gotten into the 22Rv1 cell line? As the work progressed, the answer—and the origin of the virus itself—emerged.
Dr. Fan called the study a nice example of "molecular viral archeology," noting that the researchers had tracked down tumor samples in freezers around the country. In California, for instance, Dr. Pathak located a series of tumor samples from the experiment in which the tumor samples had been grown in mice and were later used to create the 22Rv1 cell line.
An important clue emerged when his lab tested the earliest samples and found no XMRV. "If the original tumor from a patient had XMRV, then all the samples derived from this tumor should have had it," said Dr. Pathak. "This was not the case."
The researchers discovered XMRV in the later samples, however, indicating that the virus must have emerged during the experiment. Without knowing the risk of contamination, nonvirology labs then handled the prostate cancer cells for a decade.
Once the virus was in the cell line, "it is not hard to imagine how it could have been spread through many labs," said Dr. Coffin, who works part of each month at NCI-Frederick and is a special advisor to the NCI director. In his lab at Tufts, Oya Cingöz, a graduate student in genetics, conducted much of the research.
Although XMRV replicates well in culture and could infect people, it is unlikely that the virus would spread easily from person to person. The reason, Dr. Fan explained in an e-mail, is that humans "have a fairly potent intracellular resistance factor that prevents XMRV infection."
On the Trail of a Mysterious Virus
In the summer of 2009, XMRV was seen as a mysterious and potentially threatening retrovirus. A few months earlier, at the annual Cold Spring Harbor Laboratory meeting on retroviruses, researchers presented a study suggesting that, if the virus were real, millions of people in the United States could be infected.
Because of the prostate cancer link and the possibility that a new retrovirus could be circulating in the population and causing disease, NCI convened a meeting of experts in July 2009.
By September, a plan and funding were in place to develop the tools and resources needed to study XMRV. Dr. Stuart Le Grice of NCI-Frederick had assembled a team of retrovirologists to apply their experience working on HIV to questions about a new retrovirus.
"We looked at XMRV from the perspective that it could be real or it could be contamination," said Dr. Le Grice. "We had no bias going in."
Less than 2 years later, the field has an answer. With the findings published, Dr. Le Grice said, it is important to remember that "there is still no evidence that this virus was ever in patients."
The findings appeared in Science along with a companion report on CFS. In that report, researchers were unable to detect evidence of XMRV in patients whose blood samples had tested positive for the virus in the original 2009 study, also published in Science.
Since then, at least 10 independent studies have also failed to detect XMRV in patients with CFS.
In an accompanying statement, the editor-in-chief of Science, Dr. Bruce Alberts, "expressed concern" about the 2009 study in Science linking the virus to CFS. The journal, he wrote, awaits the outcomes of two NIH-sponsored studies of XMRV and CFS now under way.
Last week, Dr. Dennis Mangan, who chairs a trans-NIH working group on CFS, said that these studies were expected to continue until completion.
The new reports in Science "are probably not the final word [on XMRV and these diseases], but they are definitive on where we stand at the moment," said Dr. Goff.
It is still possible, he noted, that some individuals may be infected with a virus that contributes to the diseases. Now, however, the burden of proof is on investigators to show that any virus they detect is not the result of contamination and is a contributing factor, he said.
A Cautionary Tale about Contamination
"The XMRV story is a cautionary tale about contamination," said Dr. Pathak. "And as our technology becomes ever more sensitive [for detecting the presence of mouse and viral DNA in patient samples] this will become an even bigger concern."
The XMRV story is also an interesting story of how science happens. Although Drs. Pathak and Coffin were each aware that the other was chasing down a different XMRV-like virus, they never imagined that the viruses would be the two parents of XMRV.
Good fortune played a role as well. As Dr. Le Grice noted, it is conceivable that the two labs might have discovered the same mouse virus rather than both parents, delaying their progress.
On December 17, when Dr. Coffin made the discovery, Dr. Pathak was too busy racing around to even respond to the e-mail until after he had boarded a plane. If Dr. Pathak had received the news a few days earlier, he might have postponed a 2-week vacation to a place without Internet access.
As it happened, he had a wonderful trip. And in the final moments before the flight, he managed to fire off a short reply to Dr. Coffin: "That's awesome!!"
Further reading: XMRV and Human Disease Association: Questions and Answers
Featured Clinical Trial
Combining Second-Line Targeted Therapies for Advanced Kidney Cancer
Name of the Trial
Phase III Randomized Study of Everolimus with Versus without Bevacizumab in Patients with Advanced Renal Cell Carcinoma that Progressed after First-line Treatment with Tyrosine Kinase Inhibitors (CALGB-90802). See the protocol summary.
Dr. George K. Philips, Georgetown-Lombardi Comprehensive Cancer Center and Cancer and Leukemia Group B
Why This Trial Is Important
Renal cell carcinoma (RCC) accounts for nearly 3 percent of all yearly cancer diagnoses in the United States. Once thought to be a single disease, several distinct subtypes are now recognized, including clear cell, papillary/chromophilic, chromophobic, and collecting duct carcinomas. Each of these subtypes has a unique genetic basis and susceptibility to targeted therapies. Nevertheless, some RCC tumors may have features of more than one subtype.
Standard treatment for localized RCC includes surgical removal of part or all of the affected kidney, the adjacent adrenal gland, and nearby lymph nodes. Up to 30 percent of patients, however, have metastases at the time of diagnosis, and another 30 percent of those treated for localized disease will relapse. Since RCC is known to be resistant to standard chemotherapy drugs, patients must rely on alternative systemic therapies.
Until the middle of the last decade, biological therapy with high-dose interleukin-2 or interferon, both of which have substantial toxicities, was the only option available to patients with advanced RCC, and only a small percentage of patients had a positive response to these treatments. In 2004, researchers showed that clear cell RCC tumors respond to the tyrosine kinase inhibitor (TKI) sorafenib and, subsequently, to other TKIs, including sunitinib and pazopanib. But after initially responding to TKIs, RCC tumors began to develop resistance to the drugs, necessitating the identification of new second-line therapies.
In 2009, the FDA approved everolimus, an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway, and interferon-alpha plus bevacizumab (Avastin), an anti-VEGF monoclonal antibody, for the treatment of advanced RCC. These treatments were shown in separate randomized clinical trials to increase progression-free survival but not overall survival.
The goal of this new clinical trial is to determine whether using everolimus and bevacizumab in combination will improve the overall survival of patients with RCC whose disease has progressed on TKIs. The trial is accepting participants who have metastatic RCC with some component of clear cell disease, have cancer that has progressed after treatment with at least one prior TKI, and have not been previously treated with a VEGF-binding agent or an mTOR inhibitor. Participants will take oral everolimus once a day and be randomly assigned to receive either intravenous bevacizumab or a placebo twice a month. Doctors will monitor the participants to determine whether the combined treatment helps extend overall survival and progression-free survival and to evaluate the toxicity of the combination.
"This trial is an example of a sequential hit to an angiogenesis pathway," said Dr. Philips. "One is the mTOR inhibitor blocking the production of its downstream target VEGF, and the other, bevacizumab, hammering down the actual VEGF levels. Essentially, it is a two-pronged attack to reduce VEGF levels as much as possible.
"There is a vacuum in what to do for kidney cancer patients after failure of a first-line TKI," he continued. "We want to move this field forward and have some good data to base clinical decisions on and to know that we are improving the outcome of patients with kidney cancer."
Cancer Advocates at ASCO: Connecting for a Cause
The two oncologists took their seats at the front of the U-shaped row of chairs. Each of those chairs was occupied by a cancer advocate, eager to hear the experts' opinions about some of the major research presented earlier in the day at the American Society of Clinical Oncology (ASCO) annual meeting.
For the doctors, Andrew Seidman of Memorial Sloan-Kettering Cancer Center and Sonali Smith of the University of Chicago, it was a polite peppering.
Shirley Mertz, a breast cancer survivor who serves on an advisory board to the NCI-supported breast cancer Specialized Program of Research Excellence at the University of Chicago, wanted to know about the results from a study in which levels of circulating tumor cells were correlated with the prognosis of patients being treated for prostate cancer. Could such measurements, she asked with some concern, be used in the future to deny patients care?
Musa Mayer, a breast cancer advocate with AdvancedBC.org, wondered whether the women called "high-risk" in an ovarian cancer clinical trial had been a predefined group. The trial results suggested that high-risk patients survived longer with the cancer drug bevacizumab (Avastin). But if the analysis of this specific subgroup had not been planned in advance, she warned, that could very well influence any potential regulatory decisions by the Food and Drug Administration.
One by one, they approached the tall microphone in the middle of the U and delivered question after probing question. Dr. Seidman, who earlier in the day had moderated a press briefing with a room full of often-skeptical journalists, was clearly impressed.
"You ask better questions than reporters from the Wall Street Journal, CNN, and Bloomberg," he quipped.
Connecting with Researchers and Other Advocates
Held at the end of the day on Saturday and Sunday, the scientific review sessions are perhaps the highlight of ASCO's official advocacy program. The sessions offer an opportunity for the advocates in attendance—most at their own expense—to learn even more about the progress being made against cancer, directly from cancer researchers.
Advocates can get a reduced registration fee and scholarships to help cover the cost of attending, explained Jeannine Salamone, a two-time breast cancer survivor who directs ASCO's advocacy relations program. About 350 advocates attended this year's meeting.
Many advocates spend their time at the 5-day meeting attending educational sessions or trawling through the poster abstracts in the cavernous exhibit hall for gems of information about their cancers or their causes. But attending the meeting is not just about education. It's also about action. A quick rundown of Valerie Guild's itinerary makes that clear.
Nearly every day of the meeting her schedule is booked solid. In addition to attending scientific sessions, Guild, who founded AIM at Melanoma 7 years ago, will meet with representatives from pharmaceutical companies to discuss their research efforts and upcoming trials, with academic researchers to follow up on their investigations, and with staff from other advocacy groups about potential or current collaborative efforts.
Guild, whose 25-year-old daughter died only 9 months after being diagnosed with advanced melanoma, rattled off drug names and trial acronyms with ease, clearly comfortable with the complex jargon of the oncology research world. For her, the meeting is a one-stop shopping extravaganza where progress toward many aims can be made in a short period.
"It's the one time of the year where anybody you want to find, you can find," she said. Having attended five previous ASCO annual meetings, Guild says she now understands how to make the most out of one of the largest medical research conferences in the world. The first year or two was a different story.
"It was definitely daunting," she says. "I wasn't familiar with the people in the field, the physicians, the companies. So I spent a lot of time in the advocacy lounge, talking to and getting guidance from other advocates in other disease areas."
For all of the advocates, but perhaps more so for those coming to the meeting for their first or second time, the advocates' lounge is a respite from the meeting's hectic pace. It's an oasis of sorts—a place where advocates can relax, get a snack, and talk with others. It's also the hub of advocate activity at the meeting.
"The advocacy lounge is such a wonderful place to network," said Elda Railey, co-founder of the Research Advocacy Network (RAN). "What happens in those moments in the lounge is invaluable."
Taking Knowledge Back to the Community
Railey and her organization are powerful proponents of advocates attending the ASCO annual meeting, and they put their resources behind it. Every year they send a group of advocates to the meeting on scholarships that cover the costs of registration, travel, food, and lodging. Before the meeting, scholarship recipients undergo training, including scientific Webinars led by top researchers, to help them get the most out of the meeting. In return, the advocates commit to working with an organization in their community to disseminate what they have learned. This year, 15 advocates attended the meeting on RAN scholarships.
"The goal is for the advocates to take the cutting-edge science presented at the meeting and bring it back to the patient constituency in their community," Railey explains.
Taking a break in the advocates' lounge, Susan Leighton of Huntsville, AL, a 13-year survivor of ovarian cancer, explained that she was attending this year's ASCO meeting on a RAN scholarship. As an older man in a white hooded sweatshirt tapped away on an iPad at the table behind her, occasionally dipping his hand into a bag of pretzels, Leighton, who helped establish the Lilies of the Valley Foundation, recounted her lobbying efforts on the local, state, and federal level for ovarian cancer research funding.
She didn't hide her concern—you might say anger—about the prospect of cuts in cancer research funding. She easily rattled off ovarian cancer incidence and mortality figures, and recounted data from a poster presentation she attended earlier about a spouse's powerful influence on a patient's participation in clinical trials.
"I'm obviously passionate about what I'm doing," she said.
Down in the Hall
The advocates' presence was also felt in the exhibit hall. Given prime real estate by ASCO near the hall's front entrance, advocates from 20 organizations staffed individual stalls in a large oval exhibit, as well as a nearby row of booths from 30 more organizations.
The organizations run the gamut, from survivorship-focused groups to those advocating for common or rare cancers. An example of a rare-cancer advocacy group is the 4-year-old Cholangiocarcinoma Foundation, whose booth was staffed by the organization's director of advocacy, Marion Schwartz.
Speaking over the intense buzz of the crowds and videos playing on the too-many-to-count plasma screens in the hall, Schwartz recounted the challenge of advocating for such a rare cancer, with an incidence of only 2 or 3 cases per 100,000 people. She couldn't say enough, however, about the unique opportunity the exhibit space provided for talking to physicians at the meeting and letting them know about the resources available through her foundation.
"When we first started exhibiting, most of the people who stopped by the booth didn't even know we existed," she said. After a few years, that has changed. "I think physicians really understand that we can help their patients," she said.
Achieving Their Goals
The decision to come to the ASCO meeting depends on the goals of the individual advocate or advocacy organization, said Nancy Roach, who has been involved in cancer advocacy since the mid-1990s and founded Fight Colorectal Cancer in 2005.
With her elbows perched on her knees as she sat in one of the large cushioned chairs in the advocates' lounge, Roach pointed to two of her colleagues, Kate Murphy and Pam McAllister, who come to every ASCO meeting to soak up the science. Murphy blogs about new research findings on the organization's Web site.
For organizations and individuals whose chief aim is to support new research, attending the meeting is important "because you really get exposed to the science," Roach said. "And more importantly, you can get face time with the scientists, which allows you to better evaluate the science and contribute more effectively."
But for many of the advocates, coming to the ASCO meeting is about providing immediate help to those who need it. "You can come here and learn the science," Leighton said. "And then you can really help the patients and survivors who want to understand it."
Having that information, she continued, may "help guide them in making educated treatment decisions with their physicians."
FDA Announces Changes to Sunscreen Labels
The Food and Drug Administration (FDA) has announced that sunscreen products meeting modern standards for effectiveness may be labeled with new information to help consumers find products that reduce the risk of skin cancer and early skin aging, in addition to helping prevent sunburn.
The regulation allows sunscreens that pass the FDA's test for protection against ultraviolet A (UVA) and ultraviolet B (UVB) radiation to be labeled as "broad spectrum." UVA and UVB radiation contribute to sunburn, skin cancer, and premature skin aging. Sunburn is primarily caused by UVB radiation.
Under the new rules, manufacturers of sunscreens labeled as broad spectrum and SPF 15 or higher may state that the products will help prevent sunburn and reduce the risk of skin cancer and early skin aging. Products that have SPF values between 2 and 14 and pass the FDA's test may be labeled as broad spectrum, but the manufacturers may not state that these products reduce skin cancer risk or early skin aging.
Any product that is not broad spectrum, or that is broad spectrum but has an SPF between 2 and 14, must carry a warning stating that the product has not been shown to help prevent skin cancer or early skin aging.
More information on sunscreens is available from the FDA online.
No Link Found between Hypertension Drugs and Cancer
After reviewing data from 31 randomized clinical trials, the FDA has concluded that angiotensin receptor blockers (ARBs)—drugs that are used to treat high blood pressure—do not increase the risk of cancer.
The FDA announced last July that it would perform a safety review of ARBs after a published analysis of five randomized clinical trials with roughly 62,000 participants found a small but statistically significant increased risk of cancer in patients taking the drugs.
The FDA's more comprehensive analysis of 31 trials with about 156,000 participants showed no increased risk of cancer among patients taking ARBs. In addition, the FDA's analysis found no evidence of an association between ARBs and cancer-related death.
For more information, see the FDA's news release.
Thermography Is No Substitute for Mammography, FDA Warns
The FDA is advising women and doctors not to be misled by claims that thermography—a technique that uses infrared light to identify patterns of heat and blood flow near the body's surface—can be used as a stand-alone tool to detect breast cancer.
"The FDA is not aware of any valid scientific data to show that thermographic devices, when used on their own, are an effective screening tool for any medical condition, including the early detection of breast cancer or other breast disease," the agency stated in an alert issued June 2.
So far this year, the agency has issued three warning letters to practitioners and manufacturers of thermography devices for claiming that the technique can replace mammography.
"Mammography is still the most effective screening method for detecting breast cancer in its early, most treatable stages," Dr. Helen Barr, director of the Division of Mammography Quality and Radiation Programs in the FDA's Center for Devices and Radiological Health, said in a press release.
"While there is plenty of evidence that mammography is effective in breast cancer detection, there is simply no evidence that thermography can take its place," Dr. Barr continued.
Thermography devices have been cleared by the FDA for use as an adjunct, or additional, tool for detecting breast cancer. No randomized clinical trials, the gold standard for demonstrating effectiveness of a medical treatment or diagnostic test, have assessed the ability of thermography to detect breast cancer.
NCI Director Announces New Staff Appointments
NCI Director Dr. Harold Varmus recently announced staff appointments to several key positions in the institute.
Dr. James Doroshow has taken on a new role as NCI deputy director for Clinical and Translational Research. He had been the director of the Division of Cancer Treatment and Diagnosis (DCTD) since 2004, and he brings tremendous institutional and scientific knowledge about clinical investigation to his new position. DCTD will be jointly managed by current DCTD Deputy Director Dr. Joe Tomaszewski and DCTD Cancer Therapy Evaluation Program (CTEP) Director Dr. Jeff Abrams.
Dr. Barbara Wold will join NCI as director of the new Center for Cancer Genomics for a year while she is on leave from her position as Bren Professor of Molecular Biology and director of the Beckman Institute at the California Institute of Technology. A member of the Caltech faculty since 1981, Dr. Wold brings experience and insight from her work developing innovative tools in bioinformatics, such as RNA-Seq (a method for mapping and quantifying mammalian transcriptomes), and her discoveries in molecular genetics, genomics, and the regulation of cell fate. She will begin her new assignment on September 1.
Dr. Ted Trimble, head of Gynecological Cancer Therapeutics in CTEP, is serving as acting director for the new NCI Center for Global Health. He was instrumental in developing the trans-NCI International Clinical Trials Collaboration Working Group, and he has other global health experience that will be helpful in launching the new center.
Science Applications International Corporation (SAIC) has selected Dr. David Heimbrook as chief executive officer of SAIC-Frederick, Inc., an NCI partner. Dr. Heimbrook, previously the global head of discovery for the Oncology Discovery and Translation Area of Hoffman-LaRoche, Inc., began his new duties May 31.
Abstracts Sought for Annual Molecular Markers in Cancer Meeting
The Fifth EORTC-NCI-ASCO Annual Meeting on "Molecular Markers in Cancer" will be held October 27–29 in Brussels, Belgium.
This year, the program will focus on challenges in biomarker development for clinical application in the age of multiplex testing and genome-wide screening. Topics also include molecular imaging, drug resistance, and emerging pathways for targeted therapeutics of novel molecular entities. Abstracts must be submitted by 8:00 a.m. ET on June 21.
A 2-day diagnostic development tutorial for early-career oncologists and scientists will precede the meeting. Early-career oncologists and scientists are eligible for a grant covering tutorial and meeting fees, lodging, and travel. The application deadline for the grant is June 15.
Research to Reality Cyber-Seminar Will Feature Community Impact Program
To mark National Survivorship Day, NCI's June 21 Research to Reality (R2R) cyber-seminar will highlight LIVESTRONG's Community Impact Project (CIP), an innovative approach for expanding the organization's community grants program. The seminar will explore the dissemination of one of LIVESTRONG's 2010 CIP survivorship programs, SuperSibs!
NCI Cancer Classroom Webinar Series Continues June 28
NCI's Office of Communications and Education is midway through a free, four-part webinar series, Cancer Classroom, for early-career public health professionals or those new to the field of oncology. This series provides the educational guidance, tools, and resources necessary for professionals to address cancer as a public health issue. The remaining sessions cover the clinical trials process.
The workshops are free, but preregistration for each session is required. To register or learn more, visit the NCI Cancer Classroom Series Web site. The remaining workshops will take place on Tuesdays from 2:00 p.m. to 3:30 p.m. ET on the following dates:
- June 28–Clinical Trials 101
- July 26–Clinical Trials 102
If you missed the first two sessions, view them online: