CURExtra - Making Progress: 2007 in Review

Each year the American Society of Clinical Oncology, the largest organization of cancer professionals in the world, publishes Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, detailing the year’s most significant cancer research.

The 2007 report, which can be viewed on ASCO’s patient website, People Living With Cancer ( www.plwc.org), identified the top six advances, along with 18 others in fields such as cancer survivorship and prevention. Here, in no particular order, are five of those advances and what they mean for you.

ADVANCE 1: First Drug Approved for Primary Liver Cancer

Although researchers have made huge strides in cancer treatment in the past few decades, liver cancer remains largely untamed when it cannot be surgically removed, resisting standard treatments like chemotherapy. A recent highlight came with the approval of a targeted agent called Nexavar (sorafenib) for advanced liver cancer after a phase III study found the drug extended survival.

While liver cancer is common on a global scale—close to 700,000 cases worldwide—it remains comparatively rare in the United States, with about 19,000 Americans diagnosed in 2007. But incidence has been rising over the past two decades and is expected to continue its climb for at least a couple more decades.

Studies show chemotherapy offers little, if any, survival benefit and poses a high risk of side effects. One reason for chemotherapy’s ineffectiveness is cirrhosis, a permanent scarring of the liver resulting from diseases that repeatedly injure and kill normal liver cells over a long period of time.

Cirrhosis impacts the liver’s ability to metabolize cancer drugs, rendering them ineffective. Other treatments, such as surgery and radiofrequency ablation, which uses heat to destroy tumors, are usually reserved for early-stage disease.

Nexavar’s approval was based on phase III results of an international placebo-controlled trial, known as the SHARP trial, in more than 600 patients with inoperable primary liver cancer. Results were presented at the 2007 ASCO meeting and showed Nexavar extended survival in patients with advanced disease. The SHARP trial was stopped early after a planned early analysis showed a significant overall survival advantage in patients receiving Nexavar.

Patients on Nexavar had a median overall survival of 10.7 months compared with 7.9 months in patients taking placebo. Another analysis showed Nexavar also slowed tumor progression. Common side effects of Nexavar include fatigue, diarrhea, and rash.

Nexavar, first approved in late 2005 for a common type of kidney cancer, is a multikinase inhibitor that slows the uncontrolled growth of cancer cells and disrupts the blood supply that feeds the tumor.

Read about Nexavar’s approval in Winter 2007’s Drugs in the News. And read CURE’s comprehensive coverage of primary liver cancer in the Spring 2007 issue.

ADVANCE 2: Hormone Replacement Therapy Linked to Breast Cancer Drop

Breast cancer rates increased throughout the 1990s before making a clear downward turn around 2003—about 14,000 fewer women were diagnosed with breast cancer that year than in the year before. The nearly 7 percent overall drop included a 15 percent drop in estrogen receptor-positive breast cancer, which makes up about two-thirds of all breast cancers.

Many researchers pointed to the Women’s Health Initiative, a research study that was stopped early in 2002 after investigators determined the group taking estrogen plus progestin hormone replacement therapy for at least five years had a 26 percent greater risk of breast cancer than women taking placebo. The subsequent fallout resulted in 38 percent of all women who were prescribed HRT to stop taking it.

At the San Antonio Breast Cancer Symposium in late 2006, Peter Ravdin, MD, PhD, a research professor in the Department of Biostatistics at M.D. Anderson Cancer Center in Houston, presented an analysis that he and colleagues say statistically shows the 6.7 percent drop in breast cancers between 2002 and 2003 was primarily the direct cause of the WHI findings.

However, not all experts were as quick to point to the WHI results as the only cause. Mammography rates had been decreasing around that time, leading many to conclude that fewer diagnoses were being made.

But in April 2007, Dr. Ravdin and colleagues, using recently released data on 2004 cancer incidence, reported in the New England Journal of Medicine that despite a continued decline, breast cancer cases appeared to be leveling off after the significant drop between 2002 and 2003. The M.D. Anderson researchers say that although causality cannot be definitively proven between HRT and breast cancer, the numbers show “a very compelling link” between the two.

Read CURE’s detailed report on the link between HRT and breast cancer in Fall 2007’s cover story.

ADVANCE 3: Preventive Radiation Delays Lung Cancer Spread to the Brain

While non-small cell lung cancer (NSCLC) makes up the majority of lung cancer cases, small cell lung cancer (SCLC) makes up about 20 percent and is more aggressive with fewer treatment options. As with NSCLC, most SCLC patients are diagnosed with late-stage disease, after the cancer has spread outside the lung. Patients commonly develop brain metastases within two years of diagnosis.

To reduce brain metastases in this hard-to-treat cancer, an international study of 286 advanced SCLC patients who responded to chemotherapy were given prophylactic cranial irradiation (PCI). After one year, only 14.6 percent of patients treated with PCI had symptoms of brain metastases compared with 40.4 percent of patients in the control group.

Overall survival doubled, with 27.1 percent of patients still alive after one year compared with 13.3 percent in patients who didn’t receive PCI.

Side effects of PCI include headache, nausea and vomiting, and fatigue. Additional data will be presented later this year, but researchers predict PCI will become standard practice for patients with advanced SCLC.

For more about this study, read CURE’s coverage of ASCO’s 2007 annual meeting in the Summer issue.

ADVANCE 4: HPV Linked to Head and Neck Cancers

The link between cervical cancer and human papillomavirus, or HPV, has become the catalyst for at least two preventive vaccines (Gardasil is approved; Cervarix is currently under review). New research now shows vaccinating against HPV may also prevent a flurry of other cancers, including head and neck, vulvar, and anal cancers.

Sexually transmitted HPV is so common that 75 percent of sexually active women have been exposed to it at some point. Most women, however, never develop cancer because while there are more than 100 types of HPV, only about 15 have been linked to cancer, including types 16, 18, 31, and 45.

Scientists found HPV is associated with 10 to 20 percent of mouth cancers and about half of all cancers of the back of the mouth (oropharyngeal), including the base of the tongue and throat.

Among 100 newly diagnosed oropharyngeal patients, researchers found oral HPV type 16 in 72 percent of tumor samples, regardless of past tobacco and alcohol use—a primary risk factor of non-HPV-associated head and neck cancers. In the May 2007 issue of the New England Journal of Medicine, the study’s authors encouraged vaccination against oropharyngeal cancers: “Our results and those of other studies provide a rationale for HPV vaccinations in both boys and girls—since oropharyngeal cancer occur in men and women.”

More recently, in a February 2008 issue of the Journal of the National Cancer Institute, researchers reported patients with HPV-positive head and neck cancer fared better with chemotherapy than patients with HPV-negative cancer, with response rates of 84 percent and 57 percent, respectively. Two-year overall survival was also higher in the HPV-positive cancers at 95 percent compared with 62 percent.

CURE examined HPV’s association with cervical cancer in Winter 2004.

ADVANCE 5: Breast MRI Better for High-Risk Women

In mid-2007, the American Cancer Society issued new guidelines on breast cancer screening based on a study that showed certain populations benefit from magnetic resonance imaging (MRI) in addition to mammography, including women with a strong family history of breast cancer and those who had radiation therapy to the chest for treatment of Hodgkin’s disease.

In addition, a recent New England Journal of Medicine study found that for women diagnosed with breast cancer in one breast, MRI could detect cancer missed by mammography and clinical examination in the other breast. Nearly 1,000 women examined in the study had a recent diagnosis of unilateral breast cancer with no suspicious abnormalities in the other breast. Using MRI, 18 women were found to have cancer in the other breast. It is still controversial if all women with breast cancer need MRI to detect occult cancers in the same or the other breast.

Read CURE’s 2007 coverage of breast cancer screening in “Advances in Breast Cancer: A Special Issue.”

More Progress Ahead

Other notable advances include the success of Avastin (bevacizumab) in treating advanced kidney cancer, axitinib’s promising results in advanced thyroid cancer, and a newer approach to radiation for breast cancer called hypofractionated radiation that allows for larger doses each day so that the total course can be completed in about half the time.

To continue making advances in cancer research, ASCO stressed in its report that a greater emphasis should be placed on increasing federal funding for research and improving clinical trial enrollment, including lifting barriers for patient participation by mandating insurers to increase coverage for routine care during clinical trials.