The 2013 American Society of Clinical Oncology Annual Meeting

TON - July 2013 Vol 6 No 6 — July 29, 2013

The 2013 American Society of Clinical Oncology (ASCO) Annual Meeting brought approximately 30,000 cancer specialists to Chicago, Illinois, from May 31 to June 4, 2013. The theme of this year’s meeting was Building Bridges to Conquer Cancer. More than 4500 abstracts were available to scientists, oncologists, and healthcare workers involved in clinical research. Following are some of the highlights from ASCO 2013.

HPV Oropharyngeal Cancer Risk in Spouses of Patients

Spouses and partners of patients with human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) can gain reassurance from a study showing that they did not have an increased risk of HPV-related cancer. Most patients with HPV-OPC are male, and their spouses/partners have a great deal of anxiety over whether they are likely to also develop the cancer.

"The Human Papillomavirus Oral Transmission Study in Partners Over Time [HOTSPOT] is the first study to examine oral HPV prevalence among spouses of HPV-positive OPC patients. Patients and their spouses worry about oral HPV transmission and wonder about the risk of cancer for the spouses. These findings show that prevalence of oral HPV infection is not increased among spouses, and their risk of developing an HPV-related oral cancer is low,” said lead author Gypsyamber D’Souza, PhD, MPH, MSA, of Johns Hopkins University in Baltimore, Maryland. “Long-term couples have already shared whatever infections they have, and no changes in their physical intimacy are required,” she added.

The pilot study enrolled 166 patients with HPV-OPC and 94 spouses/long-term partners. The test for HPV was an oral rinse/gargle sample to measure HPV DNA, which is a research test with imperfect sensitivity and specificity, D’Souza explained. Of the 166 patients, 147 were men and 19 were women. Median age was 56 years.

The study found that 65% of patients had HPV detected at diagnosis, and 7% still had HPV infection 1 year after cancer treatment. The overall prevalence of HPV infection among partners was 7.2%. The prevalence among the female partners was 5%, which is similar to women in the general population. HPV-16, the subtype responsible for most cases of HPV-OPC, was detected in 54% of patients but only 2.7% of the 88 female partners and none of the 6 male partners.

A history of oropharyngeal cancer in partners was uncommon. None was detected in partners in an oral cancer screen. Five (3.4%) of the male patients reported having a partner who developed cervical cancer or precancer; a history of cervical cancer was reported in 1 current partner and 2 previous partners; a history of cervical dysplasia was reported in 2 current partners of HPV-OPC cases.

"Men have a higher prevalence of HPV-OPC than women. Maybe they are more likely to get HPV, and there may be some environmental differences. We don’t know how HPV is transmitted. Oral sex most likely transmits it to the mouth, but there is no evidence that saliva transmits it to the genitals,” D’Souza said.

Reference
D’Souza G, Gross ND, Pai SI, et al. Oral HPV infection in HPV-positive oropharyngeal cancer cases and their spouses. J Clin Oncol. 2013;31(suppl):Abstract CRA6031. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

 

Selumetinib Improves Outcomes in Uveal Melanoma

Selumetinib achieved tumor shrinkage in half of patients with melanoma of the eye (uveal melanoma) and doubled progression-free survival (PFS) compared with temozolomide in a phase 2 crossover study, making this the first agent to improve clinical outcomes in this relatively rare type of cancer.

“This is the largest randomized study of patients with melanoma of the eye, and selumetinib more than doubled progression-free survival compared with temozolomide,” said lead author Richard D. Carvajal, MD, of Memorial Sloan-Kettering Cancer Center in New York City.

Temozolomide was selected as the comparator agent for the study. Although the drug is used for cutaneous melanoma, it has no known effect in uveal melanoma. Carvajal said the choice of a comparator drug was challenging because there is no known effective therapy in uveal melanoma. The standard of care is participation in clinical trials, he noted.

“The choice of comparator drug was discussed, and we felt that temozolomide was a reasonable choice,” he told listeners at an ASCO press conference. About 2000+ cases of uveal melanoma are diagnosed each year in the United States. Most patients present with early-stage disease, but about 50% develop metastatic disease, with a median survival of 9 to 12 months.

Selumetinib is an oral MEK inhibitor; MEK is a key component of the mitogen-activated protein kinase (MAPK) pathway. Alterations in GNAQ and GNA11 activate the MAPK pathway, leading to cancer cell proliferation. These mutations are present in about 85% of patients with uveal melanoma and render them susceptible to MEK inhibition.

In the study, 98 patients with treatment-naive uveal melanoma were randomized to receive, in a 1:1 ratio, oral temozolomide 150 mg/m2 daily or oral selumetinib 75 mg twice daily for 5 days in a 28-day cycle. If the disease progressed, patients receiving temozolomide were allowed to cross over to selumetinib. During the study, 40 of the 44 patients (90%) in the temozolomide arm with radiographic progression crossed over to selumetinib.

Both arms were well balanced at baseline for age, sex, performance status, disease stage, and previous therapies. More than 90% had metastatic disease (most having liver metastases), and more than 50% had elevated lactate dehydrogenase levels. GNAQ mutations were present in about 37% of both arms; GNA11 mutations were seen in 50% of the temozolomide arm and 44% of the selumetinib arm; wild-type EXON5 was present in 14% and 19%, respectively.

On a waterfall plot, tumor regression was achieved in 50% of the selumetinib group versus 11% of the temozolomide group; 15% and 0%, respectively, had a RECIST response.

PFS was 15.9 weeks in the selumetinib arm versus 7 weeks in the temozolomide arm, a difference that was highly significant (P = .0005). Median overall survival was not significantly different at the time of ASCO, 10.8 months versus 9.4 months, respectively.

“Selumetinib could be considered a new standard for patients with advanced uveal melanoma and provides a platform for the development of new combination approaches,” Carvajal stated.

Reference
Carvajal RD, Sosman JA, Quevedo F, et al. Phase II study of selumetinib (sel) versus temozolomide (TMZ) in gnaq/Gna11 (Gq/11) mutant (mut) uveal melanoma (UM). J Clin Oncol. 2013;31(suppl):Abstract CRA9003. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

 

Simple Rapid Vinegar Cervical Test Saves Lives in India

A simple low-tech intervention delivered by women from the slums in India reduced the rate of death from cervical cancer in that country by about one-third. The intervention, which entails visual inspection of the cervix after a swab of vinegar is applied to it, could prevent an estimated 22,000 deaths from cervical cancer in India annually and close to 73,000 deaths each year in the developing world.

“Cervical cancer is the number one cause of cancer related death in India and in most parts of the developing world. But in the developed world, the incidence has declined due to screening. There is no cancer screening program in India, and Pap screening is not feasible because of inadequate infrastructure, cost, and other factors,” explained lead author Surendra Shastri, MD, of the Tata Memorial Centre in Mumbai, India.

The study included more than 150,000 women, aged 35 to 64 years with no previous history of cancer, from 20 slum clusters in the state of Maharashtra. The women were randomized to receive either screening with visual inspection with vinegar (VIA) to the cervix (n = 75,360) or no screening (n = 76,178). Primary healthcare workers were recruited from the slums and given a 4-week training on VIA to deliver the intervention.

The VIA test takes 1 minute for results: after vinegar is applied to the cervix, if white areas appear in or near the transformation zone on the endocervix and/or ectocervix, the test is considered VIA positive; if not, it is VIA negative.

Both groups were provided with cancer education and biennial monitoring for cervical cancer; the screening group also had 4 rounds of biennial VIA screening. In both groups, women were referred to the Tata Memorial Hospital for diagnosis and for free treatment if cases of cervical intraepithelial neoplasia or invasive cervical cancer were confirmed.

The incidence of cervical cancer was similar in the 2 groups: 26.7 per 100,000 in the screening group and 27.5 per 100,000 among controls. Thus, VIA screening did not lead to overdiagnosis.

Cervical cancer–specific death rates were reduced by 31% with VIA screening (P = .003); these rates were 11.1 per 100,000 in the screening group and 16.2 per 100,000 in controls. There was also a nonsignificant 7% reduction in all-cause mortality in the screened group.

Shastri and colleagues plan to train primary healthcare workers to provide VIA screening every 24 months to all women between the ages of 35 and 64 years in Maharashtra state. In addition, the Indian government is planning to implement VIA screening throughout the country and to work with other countries in the developing world to offer training resources.

Reference
Shastri SS, Mittra I, Mishra G, et al. Effect of visual inspection with acetic acid (VIA) screening by primary health workers on cervical cancer mortality: a cluster randomized controlled trial in Mumbai, India. J Clin Oncol. 2013;31
(suppl):Abstract 2. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

 

Modafinil No Help With Fatigue in Lung Cancer

A phase 2 study had previously shown that modafinil and placebo significantly relieved fatigue in patients with lung cancer. This lack of significant differences between treatment groups called into question National Comprehensive Cancer Network (NCCN) recommendations for the treatment of cancer-associated fatigue.

In a recent multicenter double-blind phase 4 trial, 208 patients with lung cancer were randomized to receive, in a 1:1 ratio, modafinil or placebo. Modafinil was given at a dose of 100 mg for 14 days, followed by 200 mg for 14 days.

Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue survey. A 3-point change in the FACIT-fatigue score is believed to be clinically significant.

At 28 days, patients receiving modafinil had a mean change of 5.28 points on the FACIT-fatigue scale compared with 5.11 points in those receiving placebo, a nonsignificant difference. Most responses were observed at day 14 and sustained through the end of the study, indicating no dose-dependent response.

No differences between groups were noted on secondary end points assessed using the Epworth Sleepiness and Hospital Anxiety and Depression scales. Adverse events were also similar between groups. These included headache, nausea/vomiting, and anxiety (symptoms commonly associated with modafinil).

The study was presented by Kate Fife, MD, of the NIHR Cambridge Biomedical Research Centre in the United Kingdom.

This is the second placebo-controlled study to call into question use of psychostimulants to control cancer-related fatigue. l

Reference
Fife K, Spathis A, Dutton SJ, et al. A multicenter, randomized, double-blinded, placebo-controlled trial of modafinil for lung cancer-related fatigue: dose response and patient satisfaction data. J Clin Oncol. 2013;31
(suppl):Abstract 9503. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

 

Being Fit at Age 50 Lowers Cancer Risk

Middle-aged men with a high level of cardiovascular fitness have a lower risk of developing and dying of lung or colorectal cancer than do men who are not fit. Improved fitness level also reduces the risk of prostate cancer–related death but not the risk of developing it. As would be expected, men who were more fit had a lower risk of cardiovascular death.

The study measured fitness as a marker of future cancer risk. Fitness level is a different measure than body weight or exercise level, explained lead author Susan Lakoski, MD, assistant professor of internal medicine at the University of Vermont in Burlington.

“This is the first study to explore fitness as a marker of future cancer risk prognosis. This finding makes clear that patients should be advised that they need to achieve a certain level of fitness, and not just be told that they need to exercise. Unlike exercise behavior, fitness level can be measured objectively in a clinical setting. Previous studies have shown that poor fitness level is associated with increased risk of cardiovascular disease,” she said.

She recommended that primary care doctors go beyond a prescription for exercise and advise their patients that being fit lowers their risk of dying of the 3 major cancers that affect men in the United States.

The Cooper Center Longitudinal Study, conducted at the Cooper Clinic in Dallas, Texas, enrolled 17,049 men and followed them prospectively. The men had a single cardiovascular fitness assessment as part of a preventive health checkup at a mean age of 50 years. The fitness test involved treadmill walking under conditions of changing speed and elevation. Performance on the test was measured by units of fitness called metabolic equivalents (METs). Results were divided into 5 quintiles based on fitness performance.

Medicare claims were analyzed to identify study participants who had a diagnosis of lung, colorectal, or prostate cancer. At a median follow-up of 20 to 25 years, 2332 men were diagnosed with prostate cancer, 277 with lung cancer, and 276 with colorectal cancer. Cancer deaths numbered 347, and 159 men died of cardiovascular disease (CVD).

In an analysis adjusted for smoking, body mass index, age, and other factors, the risk of a diagnosis of lung cancer was reduced by 68% in men with the highest levels of fitness versus those in the lowest quintile; the risk of colorectal cancer was reduced by 38% in the highest versus the lowest quintile for fitness. No impact of fitness was found for development of prostate cancer.

Among those who developed cancer, men at the higher levels of fitness had a lower risk of cancer-related death from all 3 cancers, as well as a lower risk of death due to CVD. Lakoski said that even a 1-MET difference reduced the risk of dying of cancer and CVD by 23% and 14%, respectively.

Men who had low fitness levels were at increased risk of cancer and CVD regardless of weight. As a result of these findings, Lakoski cautioned that fitness, not weight loss, should be emphasized to reduce risk of cancer and CVD.

Reference
Lakoski SG, Barlow C, Gao A, et al. Cardiorespiratory fitness and risk of cancer incidence and cause-specific mortality following a cancer diagnosis in men: the Cooper Center longitudinal study. J Clin Oncol. 2013;31(suppl):Abstract 1520. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

Related Items


Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: