Cetuximab Provides Slight Survival Advantage in Advanced Colorectal Cancer

Use of the targeted agent cetuximab (Erbitux) provides a small, but statistically significant improvement in overall survival in patients with colorectal cancer for whom prior therapies are no longer effective, an international research team reported last week.

In a 572-patient phase III randomized clinical trial, patients treated with cetuximab had a slightly superior overall survival rate compared to with patients treated with the best supportive care, 6.1 months vs. 4.6 months. All patients in the trial had tumors that expressed the epidermal growth factor receptor, or EGFR, a known molecular target of cetuximab, the research team reported in the November 15 New England Journal of Medicine.

"This is the first time that single-agent biological therapy has shown a survival benefit in advanced colorectal cancer," the study's lead author, Dr. Derek Jonker from the National Cancer Institute of Canada Clinical Trials Group, said in April, when the trial's results were first presented at the American Association of Cancer Research annual meeting.

Cetuximab was also associated with a small, statistically significant improvement in progression-free survival compared with the best supportive care, the authors reported. In addition, 31.4 percent of patients treated with cetuximab achieved stable disease, compared with 10.9 percent in the best supportive care group, and 23 patients on cetuximab (8 percent) had a partial response, that is, some tumor shrinkage, compared with no patients in the best supportive care group.

The research team also conducted an "exploratory analysis," Dr. Jonker explained, and found that the severity of rash seen in cetuximab-treated patients seemed to correlate with treatment response. The median survival for patients who survived at least 28 days who had a very low level rash, for example, was 2.6 months, whereas it was 4.8 months for those with a moderate rash (grade 1) and 8.4 months in those with a severe rash (grade 2).

The finding, the authors concluded, "suggests that [rash] may be a predictive marker, but this point has not been validated."

Tool Uses Three Factors to Assess Breast Cancer Risk

Researchers have proposed a simplified approach to identifying postmenopausal women at elevated risk for estrogen receptor (ER)-positive breast cancer who may benefit from preventive interventions such as the drug tamoxifen. Their approach, which uses three risk factors - age, family history of breast cancer, and previous breast biopsies - performed almost as well as the current standard risk assessment tool, which evaluates six risk factors.

The simpler tool "would be more accessible for routine and rapid prescreening in the prevention or routine care setting," they wrote in a study published online November 13 in the Journal of the National Cancer Institute.

Because many women must be screened to identify the minority who would benefit from chemoprevention, screening methods are needed that identify this minority more quickly, wrote lead author Dr. Rowan Chlebowski of Harbor-UCLA Medical Center.

Using data from the Women's Health Initiative (WHI), the researchers compared several models of predicting breast cancer risk. The widely used Gail model, which evaluates six risk factors, underestimated 5-year breast cancer incidence in the WHI population by almost 20 percent, but predicted ER-positive breast cancer more accurately than ER-negative disease. The simpler tool predicted ER-positive disease almost as accurately as the Gail model.

In an accompanying editorial, Dr. Mitchell Gail, of NCI's Division of Cancer Epidemiology and Genetics (who developed the Gail model), and colleagues noted that breast cancer incidence in the WHI was higher than in the general U.S. population and risk for ER-negative breast cancer based on family history was lower than in many other studies. "Chlebowski et al. have presented useful and important results that illustrate the promise and difficulty of estimating absolute risk in subtypes of breast cancer," they wrote, adding that additional studies are needed in women aged 50 and older and in younger women.

Decline in Adult Smoking Stalls, Rates Still High in Some Subgroups

More than 45 million Americans reported smoking in 2006, according to a report from the Centers for Disease Control and Prevention's Office on Smoking and Health published in the November 9 Morbidity and Mortality Weekly Report. The self-report data from the 2006 National Health Interview Survey were analyzed by V. J. Rock and colleagues.

The federal researchers found that about one in five adult Americans (20.8 percent) were current smokers in 2006. This figure has not changed significantly since 2004, suggesting that the previous 7-year decline has now stalled. As in previous years, the researchers found far higher smoking rates among some population subgroups, including adults without a high school diploma (26.7 percent) and people living below the federal poverty level (30.6 percent).

"The continued lack of progress in reducing adult smoking rates is a serious concern, and we need to understand and address why it is happening," said Dr. Cathy Backinger, acting chief of the Tobacco Control Research Branch of NCI's Division of Cancer Control and Population Sciences.

The study's authors suggest that among the factors responsible could be a 20.3-percent decline in funding for comprehensive state programs for tobacco control and prevention since 2002 and a near doubling of tobacco-industry marketing expenditures since 1998. In 2005, industry marketing expenditures totaled $13.1 billion; about 80 percent were devoted to price discounting strategies such as coupons or discounts for retailers that reduce the impact of tobacco tax increases on the consumer.

Analysis Indicates Letrozole, Tamoxifen Safe in Early Breast Cancer

A detailed safety analysis from a large, international clinical trial of adjuvant therapy in women with estrogen receptor-positive early-stage breast cancer indicates that the risks of cardiac events from letrozole or tamoxifen are generally low.

In a paper released early online last week by the Journal of Clinical Oncology, researchers from the trial, known as BIG 1-98, reported an overall incidence of cardiac adverse events of 4.8 percent in women treated with letrozole and 4.7 percent of women treated with tamoxifen. Women treated with letrozole were more likely to have a serious cardiac event (2.4 percent vs. 1.4 percent), such as heart failure, while women treated with tamoxifen were more likely to have a serious thromboembolic event linked to a blood clot (2.3 percent vs. 0.9 percent), such as a stroke.

"Although the overall incidence was low, patients at risk for thromboembolic disease, such as those with an antecedent history of such episodes, might consider avoiding adjuvant tamoxifen therapy," wrote the study's lead author, Dr. Henning Mouridsen from the Rigshospitalet in Denmark, and colleagues.

The BIG 1-98 trial compared adjuvant therapy using the 2 drugs in more than 8,000 women, testing 5 years of treatment with either drug alone or in combination (1 drug for 2 years and the other drug for the last 3 years). Published in December 2005, the results showed that letrozole was more effective than tamoxifen in reducing the risk of recurrence, and was particularly more effective in reducing the risk of "distant recurrence," detection of a metastatic tumor at a site far from the original tumor.

A history of diabetes and being age 55 or older were both significant predictors of the risk of a cardiac adverse event, and, they noted, continued "assessment of vascular adverse effects of highly effective adjuvant therapies such as aromatase inhibitors is important."

Given the low rate of cardiac adverse events seen in the trial, they concluded, "any excess of cardiac events on letrozole seems to be outweighed by the superior control of locoregional and distant recurrence afforded by letrozole compared with tamoxifen."

Family Program Helps Prostate Cancer Patients and Spouses Cope

A family intervention program aimed at prostate cancer patients and their spouses was shown to help the couples better manage the effects of the illness and maintain their quality of life, according to a study published online November 12 in Cancer.

The study, which was funded by NCI's Division of Cancer Control and Population Sciences, involved 235 couples who were randomized to either standard care or standard care plus a family-based intervention called the FOCUS Program. The supportive-education program consists of three 90-minute home visits by nurses and two 30-minute telephone sessions spaced 2 weeks apart and delivered between the baseline assessment and 4 months.

At 4-month follow-up, intervention patients reported less uncertainty and better communication with spouses than control patients, noted researchers led by Dr. Laurel Northouse of the University of Michigan School of Nursing. Intervention spouses reported "higher quality of life, more self-efficacy, better communication, and less negative appraisal of caregiving, uncertainty, hopelessness, and symptom distress at 4 months compared with controls, and some effects were sustained to 8 months and 12 months."

Although patients benefitted from the intervention, "the effects were far greater for their spouses," the researchers noted. "At a minimum, the findings suggest that spouses of men with prostate cancer need to be included in programs of care. Too often, they are viewed as outside observers or only as providers of care. Instead, clinicians need to recognize that spouses are affected by the cancer and to treat them as co-recipients of care."