Updates from the annual meeting of the American Society of Clinical Oncology.
The annual meeting of the American Society of Clinical Oncology was held in Chicago from June 3 to 7, attracting about 32,000 cancer researchers, physicians and representatives from pharmaceutical and biotechnology sectors from around the world to learn the latest cancer care, screening, treatment and prevention. For more coverage of the conference, go to curetoday.com/asco2011.
Pair of Melanoma Studies Usher in a New Standard of Therapy for Patients with Advanced Disease
Patients with advanced melanoma are finally seeing the benefits of research. At the plenary session, investigators revealed positive results of two advanced melanoma studies. The first presentation showed patients who received the immunotherapy drug Yervoy (ipilimumab) plus dacarbazine survived longer than patients only on dacarbazine, a decades-old chemotherapy that has limited success against the disease. While Yervoy was approved in March for patients who have progressed on prior treatments, this most recent phase 3 study shows the drug is useful for previously untreated patients, improving median overall survival from 9.1 months to 11.2. Median duration of response more than doubled from 8.1 months with dacarbazine to 19.3 months with the Yervoy combination. Side effects were similar to prior studies, which include rash and diarrhea.
The second study compared dacarbazine with the oral investigational drug vemurafenib (PLX-4032), which inhibits a specific BRAF protein mutation found in about half of all melanoma tumors. The BRIM3 study looked at 675 patients with BRAF-positive tumors and found that vemurafenib extended survival by 63 percent, improving the median six-month survival rate from 64 percent on dacarbazine to 84 percent. The median progression-free survival was also better with vemurafenib. It took 1.6 months for half of the dacarbazine group to have cancer progression, whereas 5.3 months passed before half of the vemurafenib group had seen their cancer grow—an improvement of 74 percent. Side effects of vemurafenib included rash and low-grade cutaneous squamous cell carcinomas, which are benign cancers removed by a dermatologist. Due to the promising results, the drug was submitted for Food and Drug Administration approval in May.
The studies were presented on the heels of an announcement that the two drugs will be examined as a combination therapy in an early-phase trial. —Elizabeth Whittington
Correction: An earlier version of this article incorrectly stated the submission for vemurafenib was expected later this year.Vemurafenib was submitted for approval in May.
Aromasin Reduces Breast Cancer Risk in Healthy Older Women
The highest risk factor for breast cancer is age, especially after 60 and after menopause, which is why researchers have been searching for chemoprevention that can help lower the risk of one of the most common cancers in women. While tamoxifen, and more recently Evista (raloxifene), have shown great improvement in reducing the risk of invasive breast cancer (by about 50 percent), only a small percentage of women at high risk take tamoxifen to reduce breast cancer risk, primarily due to rare but serious side effects, including stroke and blood clots. Lead investigator of the trial, Paul Goss, MD, PhD, of Massachusetts General Hospital, hopes to change that with the news that Aromasin (exemestane), an aromatase inhibitor used to prevent breast cancer recurrence, lowers the relative risk of primary invasive breast cancer by 65 percent—a greater effect than tamoxifen and Evista, and without the severe side effects. Even when non-invasive cancers (ductal carcinoma in situ) were included, the rate was a 53 percent relative risk reduction. Many symptoms were the same in the Aromasin arm versus the placebo arm, including hot flashes and fatigue. —EW
Iniparib Disappoints in Breast Cancer, But Study Results Hint at Second-Line Therapy Benefit
The much anticipated data from the iniparib study in metastatic triple negative breast cancer produced a few more answers to whether the drug works, but they weren’t the answers many were hoping for. With interest high in PARP inhibitors (a relatively new class of targeted agents) after a promising phase 2 study, the phase 3 trial quickly met accrual as patients’ and doctors’ expectations for similar results grew.
When the announcement came earlier this year that the study had not reached its goal of overall survival and progression-free survival, questions arose as to how the phase 3 data could be so different from the overwhelming positive results of the phase 2 trial. Lead investigator Joyce O’Shaughnessy, MD, of Texas Oncology in Dallas, shared that the addition of iniparib to gemcitabine and carboplatin only gained one month in median progression-free survival, and overall survival only improved from 11.1 to 11.8 months.
However, this may not be the end of the line for iniparib. When responses from newly diagnosed women were separated out from those of previously treated women, the numbers suggested another story. For reasons yet unknown, women with one to two prior treatments for advanced breast cancer seemed to improve on the drug when looking at both progression-free survival (4.2 months versus 2.9 months) and overall survival (10.8 months versus 8.1 months). Another trial will be needed to confirm these suggested findings. And with confirmation that the drug’s maker, Sanofi-Aventis, will continue testing the drug in breast cancer, another trial may not be too far off. —EW
Biomarker Reveals Who Is at Highest Risk for Neuropathy
Researchers studying peripheral neuropathy—experienced to a significant degree by about one-third of cancer patients receiving taxane chemotherapy—have identified a genetic biomarker that could predict which patients are at greatest risk of developing the condition. Taxanes, although effective at destroying cancer cells, can do temporary or permanent damage to the peripheral nervous system.
“Unfortunately, there are no established biomarkers to predict which patients will experience this toxicity prior to receiving the drug,” says Bryan P. Schneider, MD, lead author and associate director for the Indiana Institute for Personalized Medicine at the Indiana University Melvin and Bren Simon Cancer Center. In the genome-wide association study of 2,204 patients on Taxol (paclitaxel), Schneider and his team looked for variations in inherited DNA called single nucleotide polymorphisms (SNPs) while evaluating more than 1.2 million SNPs in each patient.
They then identified genetic subgroups that were more likely to develop this adverse side effect. Older patients and African Americans were much more likely to develop peripheral neuropathy, according to the study, and further research in these groups is under way. The findings may lead to a simple blood test to determine whether a patient has a high risk of developing neuropathy, allowing for better counseling, use of alternative drugs or schedules, or omission of taxanes when appropriate. —Jon Garinn
Men May Be at Greater Risk Than Women for Developing HPV-Related Cancers
A new analysis from the National Cancer Institute suggests that the number of HPV-positive oral cancers among men could rise significantly in the next decade, possibly surpassing HPV-positive cervical cancers among women.
The genital human papillomavirus (HPV) is the most common sexually transmitted infection in the U.S., according to the Centers for Disease Control and Prevention. About 20 million Americans are currently infected and about 6 million are infected each year.
Using population-based cancer registry data, the researchers found that between 1988 and 2004, oropharyngeal cancers related to HPV increased by 225 percent, with men accounting for the majority of cases. Relying on U.S. Census projections and age-period-cohort models, they projected a 27 percent rise in cases by 2020.
More than 40 types of HPV are spread during genital, oral or anal sex with an infected partner—some are low-risk (wart-causing) while others are high-risk (cancer-causing). In most cases, the body’s own immune system gets rid of HPV within about two years of infection. But if the body cannot clear the infection, it can develop into several cancers, including oropharyngeal and cervical, which is the second leading cause of cancer deaths in women worldwide.
Gardasil, the only approved vaccine for young men and women, is effective against two types of cancer-causing HPV and two types of wart-causing HPV. Cervarix is an HPV vaccine approved only for women. —JG
Avastin Continues Impressive Results in Ovarian Cancer
The phase 3 OCEANS study showed benefit with Avastin (bevacizumab) in women with a recurrence of ovarian cancer successfully treated with a platinum drug. Women with epithelial ovarian, fallopian tube or peritoneal cancers that have recurred after more than six months were given standard chemotherapy of gemcitabine and carboplatin with or without Avastin. Those in the Avastin arm continued on Avastin until their disease progressed. After a median of two years, the Avastin arm had a median progression-free survival of 12.4 months compared with the chemo-only arm of 8.4 months. Avastin cut the relative risk of disease progression in half (52 percent). Addition of Avastin also improved the incidence of tumor shrinkage, increasing from 57 percent to 79 percent. It’s still too early to show an overall survival benefit in the trial, but current data suggest Avastin may provide an advantage. This is the third large trial that shows Avastin’s benefit in ovarian cancer, and submission for FDA approval in newly diagnosed patients and for recurrent cancers is forthcoming. Researchers said next steps would be to combine Avastin with chemotherapy for cancers not responding to platinum drugs, as well as combining Avastin with PARP inhibitors, an investigational class of targeted agents that have also shown success in ovarian cancer. —EW
A One-in-a-Billion Chance at Success
What if you could count tiny particles of tumor in the bloodstream to predict whether a drug is working against cancer? Researchers in collaboration with the FDA are examining such tests as part of an effort to identify treatment efficacy to make clinical trials more efficient and less expensive, which could potentially lead to quicker FDA approvals.
The research team, led by Howard Scher, MD, of Memorial Sloan-Kettering Cancer Center in New York, investigated whether tests that trap circulating tumor cells (CTCs) could determine if patients with metastatic, castration-resistant prostate cancer responded to Zytiga (abiraterone), a drug that targets a protein in the production of testosterone, which can stimulate cancer cell growth. CTCs represent about one cell in a billion in the blood stream, Scher said.
Scher’s team examined a study of 1,195 patients in which Zytiga improved the median overall survival rate by 4.6 months. CTCs were tested in 972 patients at the beginning of the trial and at monthly intervals for three months. Researchers found a correlation in the reduction of CTCs and overall survival in patients on Zytiga.
Prostate cancer is common in older men, but the standard screening test for prostate-specific antigen (PSA) is unreliable because sometimes PSA rises even when a patient is benefiting from treatment, Scher says. Measuring CTCs may predict a better prognosis and overall survival as early as four weeks after treatment, as has already been shown in patients with advanced breast cancer receiving chemotherapy. —JG^ TOP OF PAGE