market as of a date chosen by Congress: February 15, 2007. For a new product to be substantially equivalent, the company has to demonstrate that it is not more harmful than the “predicate” product. “We’ve been making decisions since last June on products that are not currently on the market,” says Mitch Zeller, JD, director of the FDA’s Center for Tobacco Products. “But this is the first time we’ve addressed the much larger universe of products that are on the market.” In the case of the bidis, manufactured by Jash International, the company did not provide the necessary information for the FDA to make a ruling on whether they were substantially equivalent, says Zeller. Therefore, the agency could not even begin a scientific review of the products. “We will continue to make these decisions on a regular basis,” he says, explaining that the substantially equivalent determination is “complicated and technical.” The FDA must determine whether the new product has “different characteristics” than the predicate product and, if so, whether those characteristics raise different questions of public health. Zeller expects many more decisions to be announced this year and in 2015 regarding tobacco products both currently on the market and those attempting to be introduced. “I’m still waiting for the FDA to be a little more aggressive with all the new cigarette brands coming out every year,” Dr. Cummings says. “Hopefully, this ban will preview some bigger things to come.” Adds Dr. Ostroff, “There is obviously no such thing as a safe cigarette, but what’s promising is that this order is an example of the FDA exercising its legal right to regulate the sale of tobacco products on the market.”
FDA Targets Teens Another way in which the FDA is using its new authority is by launching a national public education campaign to prevent youth tobacco use and reduce the number of smokers among those aged 12 to 17 years. The “Real Cost” campaign targets 10 million individuals in that age group who have either never
smoked a cigarette or are experimenting and at risk of becoming regular smokers. The ads are airing in a wide variety of media that target this age group, including television, radio, print, social media, mall kiosks, and movie theaters. They address topics such as how smoking affects appearance, including premature skin wrinkling, gum disease, and tooth loss. Other ads highlight the addiction component by framing it in terms of “loss of control” rather than actually using the word addiction, says Zeller. The ads will be refreshed later in the year to communicate new messages. In addition, the FDA will conduct a longitudinal study of 8000 young people over a period of 3 years to determine whether the campaign has built awareness, changed attitudes and beliefs, and, eventually, changed behavior and reduced the number of young smokers. The campaign has a budget of $115 million for its first year, which is the equivalent of how much money the tobacco industry spends on advertising, marketing, and promotion in 5 days, adds Zeller. The first “Real Cost” campaign will be aimed at a general market, but the FDA also plans to develop campaigns targeted to specific vulnerable populations, including boys at risk for smokeless tobacco use and multicultural; rural; and lesbian, gay, bisexual, and transgender youth. Dr. Ostroff is encouraged by all the latest developments in this arena. “It’s a very hopeful time, and there is tremendous momentum happening in the field,” she says. “The breadth of cooperation is why we’re seeing tobacco use reduction in unprecedented numbers, particularly in states with strong tobacco control policies.”
References 1. US Department of Health and Human Services. The Health Consequences of Smoking–50 Years of Progress: A Report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2014. 2. Brennan TA, Schroeder SA. Ending sales of tobacco products in pharmacies. JAMA. 2014;311:1105-1106. DOI: 10.1002/cncr.28775
New Discoveries in Lung Cancer Highlighted at Conference
© SEBASTIAN KAULITZKI | SHUTTERSTOCK.COM
P
1598
romising therapies in lung cancer were featured at the American Association for Cancer Research-International Association for the Study of Lung Cancer Joint Conference on the Molecular Origins of Lung Cancer, held January 6 through 9, 2014, in San Diego, California. Below are a few highlights from among the studies presented.
Targeting PD-1 in NSCLC A phase 1 study found that the programmed cell death 1 (PD1) immune checkpoint inhibitor MK-3475 was well tolerated and demonstrated durable responses in patients whose nonsmall cell lung cancer (NSCLC) had worsened during or after multiple prior chemotherapies. The researchers, from the University of California at Los Angeles, found that when the
Cancer
June 1, 2014
Immunotherapy for Late-Stage NSCLC A phase 2 study found that Imprime PGG, a type of immunotherapy, substantially improved response rates and overall survival rates in patients with late-stage NSCLC. When combined with an antitumor monoclonal antibody, the drug redirects the immune system’s neutrophils and monocytes to kill antibody-targeted cancer cells. The researchers, who are from Biothera (Eagan, Minnesota), identified a subpopulation of patients with sufficient levels of an antibody that enhances binding of Imprime PGG to neutrophils and monocytes. These “antibody-positive” patients are more likely to respond to the immunotherapy. The study included 90 patients with stage IIIB or stage IV NSCLC. Among patients who received the therapy, the median overall survival for those who were biomarker positive was 16.5 months versus 9.1 months for those who were biomarker negative. None of the patients in the control group survived for 3 years after treatment, whereas 7% of the group treated with Imprime PGG did. In addition, 17% of patients in the
treatment group who were biomarker positive survived for 3 years after treatment whereas none of the biomarker-negative patients did. Randomized phase 3 trials of Imprime PGG in combination with chemoimmunotherapy for several cancers are being planned, researchers say.
E-Cigarette Use May Impact Lung Cancer Results from a preclinical study suggested that electronic cigarette (e-cigarette) exposure enhances the aggressive behavior of human lung epithelial cells that have p53 and KRAS mutations, which are often found in the airways of current and former smokers at high risk of developing lung cancer. Few studies have examined how e-cigarette use can potentially affect lung function and lung cancer, say the researchers, who are from the University of California at Los Angeles. They studied human bronchial epithelial cells with mutations in p53 and KRAS, exposing them for 4 hours to e-cigarette vapor or tobacco smoke. They observed cancerous behaviors regardless of the type of exposure, including the ability of cells to become invasive and exhibit colony formation. They also noticed that changes in gene expression after exposure to e-cigarette vapor were very similar to those changes observed when the cells were exposed to tobacco smoke. In cells with normal p53 and KRAS genes, e-cigarette vapor was toxic but did not appear to cause the cells to develop cancerous behaviors. Researchers note that because many e-cigarette users are smokers at high risk of developing lung cancer due to mutations in these genes, e-cigarettes may be harmful to them. DOI: 10.1002/cncr.28776
Screening Older Women for Cervical Cancer Saves Lives
S
creening women for cervical cancer beyond age 50 years helps to prevent the disease, according to researchers from Queen Mary University of London. Their study suggests that screening women past this age saves lives and that there are benefits for women with negative screening results to continue being screened up to age 69 years.1 The researchers examined the link between screening women aged 50 years to 64 years for cervical cancer and cervical cancer diagnosed in women aged 65 years to 83 years. Participants included all women aged 65 years to 83 years diagnosed with cervical cancer in England and Wales between 2007 and 2012 (a total of 1341 women.) Women who had not been screened beyond age 50 years had a 6-fold higher risk of being diagnosed with cervical cancer compared with those who had an adequate negative screening history at age 50 to 64 years. That amounted to 49 cancers versus 8 cancers per 10,000 women spanning a 20-year period.
Women who were screened regularly and had a positive (abnormal) screening result between the ages of 50 years and 64 years had a risk of 86 cancers per 10,000 women over a period of 20 years. The authors note that their findings may not apply to other settings and that cervical screening methods are changing with the availability of human papillomavirus testing. Nevertheless, they say that cervical screening in women aged 50 years to 64 years has a major effect on cervical cancer rates among women aged older than 50 years. They add that the protective effect of screening at these ages weakens with time and is substantially less at 15 years after the last screen.
Reference 1. Castanon A, Landy R, Cuzick J, Sasieni P. Cervical screening at age 50-64 years and the risk of cervical cancer at age 65 years and older: populationbased case control study. PLoS Med. 2014;11:e1001585 DOI: 10.1002/cncr.28777
Content in this section does not reflect any official policy or medical opinion of the American Cancer Society or of the publisher unless otherwise noted. © American Cancer Society, 2014.
Cancer
June 1, 2014
1599
© AARON AMAT | SHUTTERSTOCK.COM
protein programmed cell death-ligand 1 (PD-L1) (carried by some cancer cells) attaches to PD-1 on T cells, they are unable to attack the cancer cells. Drugs targeting PD-1, such as the antibody therapy MK-3475, can potentially reverse that effect. In the study, researchers treated 38 patients with NSCLC with MK-3475 every 3 weeks. They found that the pretreatment PD-L1 expression level may be a good predictor of response to treatment with MK-3475. The median duration without worsening of disease among the 9 responders was at least 62 weeks.
FDA Targets Teens Another way in which the FDA is using its new authority is by launching a national public education campaign to prevent youth tobacco use and reduce the number of smokers among those aged 12 to 17 years. The “Real Cost” campaign targets 10 million individuals in that age group who have either never
smoked a cigarette or are experimenting and at risk of becoming regular smokers. The ads are airing in a wide variety of media that target this age group, including television, radio, print, social media, mall kiosks, and movie theaters. They address topics such as how smoking affects appearance, including premature skin wrinkling, gum disease, and tooth loss. Other ads highlight the addiction component by framing it in terms of “loss of control” rather than actually using the word addiction, says Zeller. The ads will be refreshed later in the year to communicate new messages. In addition, the FDA will conduct a longitudinal study of 8000 young people over a period of 3 years to determine whether the campaign has built awareness, changed attitudes and beliefs, and, eventually, changed behavior and reduced the number of young smokers. The campaign has a budget of $115 million for its first year, which is the equivalent of how much money the tobacco industry spends on advertising, marketing, and promotion in 5 days, adds Zeller. The first “Real Cost” campaign will be aimed at a general market, but the FDA also plans to develop campaigns targeted to specific vulnerable populations, including boys at risk for smokeless tobacco use and multicultural; rural; and lesbian, gay, bisexual, and transgender youth. Dr. Ostroff is encouraged by all the latest developments in this arena. “It’s a very hopeful time, and there is tremendous momentum happening in the field,” she says. “The breadth of cooperation is why we’re seeing tobacco use reduction in unprecedented numbers, particularly in states with strong tobacco control policies.”
References 1. US Department of Health and Human Services. The Health Consequences of Smoking–50 Years of Progress: A Report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2014. 2. Brennan TA, Schroeder SA. Ending sales of tobacco products in pharmacies. JAMA. 2014;311:1105-1106. DOI: 10.1002/cncr.28775
New Discoveries in Lung Cancer Highlighted at Conference
© SEBASTIAN KAULITZKI | SHUTTERSTOCK.COM
P
1598
romising therapies in lung cancer were featured at the American Association for Cancer Research-International Association for the Study of Lung Cancer Joint Conference on the Molecular Origins of Lung Cancer, held January 6 through 9, 2014, in San Diego, California. Below are a few highlights from among the studies presented.
Targeting PD-1 in NSCLC A phase 1 study found that the programmed cell death 1 (PD1) immune checkpoint inhibitor MK-3475 was well tolerated and demonstrated durable responses in patients whose nonsmall cell lung cancer (NSCLC) had worsened during or after multiple prior chemotherapies. The researchers, from the University of California at Los Angeles, found that when the
Cancer
June 1, 2014
Immunotherapy for Late-Stage NSCLC A phase 2 study found that Imprime PGG, a type of immunotherapy, substantially improved response rates and overall survival rates in patients with late-stage NSCLC. When combined with an antitumor monoclonal antibody, the drug redirects the immune system’s neutrophils and monocytes to kill antibody-targeted cancer cells. The researchers, who are from Biothera (Eagan, Minnesota), identified a subpopulation of patients with sufficient levels of an antibody that enhances binding of Imprime PGG to neutrophils and monocytes. These “antibody-positive” patients are more likely to respond to the immunotherapy. The study included 90 patients with stage IIIB or stage IV NSCLC. Among patients who received the therapy, the median overall survival for those who were biomarker positive was 16.5 months versus 9.1 months for those who were biomarker negative. None of the patients in the control group survived for 3 years after treatment, whereas 7% of the group treated with Imprime PGG did. In addition, 17% of patients in the
treatment group who were biomarker positive survived for 3 years after treatment whereas none of the biomarker-negative patients did. Randomized phase 3 trials of Imprime PGG in combination with chemoimmunotherapy for several cancers are being planned, researchers say.
E-Cigarette Use May Impact Lung Cancer Results from a preclinical study suggested that electronic cigarette (e-cigarette) exposure enhances the aggressive behavior of human lung epithelial cells that have p53 and KRAS mutations, which are often found in the airways of current and former smokers at high risk of developing lung cancer. Few studies have examined how e-cigarette use can potentially affect lung function and lung cancer, say the researchers, who are from the University of California at Los Angeles. They studied human bronchial epithelial cells with mutations in p53 and KRAS, exposing them for 4 hours to e-cigarette vapor or tobacco smoke. They observed cancerous behaviors regardless of the type of exposure, including the ability of cells to become invasive and exhibit colony formation. They also noticed that changes in gene expression after exposure to e-cigarette vapor were very similar to those changes observed when the cells were exposed to tobacco smoke. In cells with normal p53 and KRAS genes, e-cigarette vapor was toxic but did not appear to cause the cells to develop cancerous behaviors. Researchers note that because many e-cigarette users are smokers at high risk of developing lung cancer due to mutations in these genes, e-cigarettes may be harmful to them. DOI: 10.1002/cncr.28776
Screening Older Women for Cervical Cancer Saves Lives
S
creening women for cervical cancer beyond age 50 years helps to prevent the disease, according to researchers from Queen Mary University of London. Their study suggests that screening women past this age saves lives and that there are benefits for women with negative screening results to continue being screened up to age 69 years.1 The researchers examined the link between screening women aged 50 years to 64 years for cervical cancer and cervical cancer diagnosed in women aged 65 years to 83 years. Participants included all women aged 65 years to 83 years diagnosed with cervical cancer in England and Wales between 2007 and 2012 (a total of 1341 women.) Women who had not been screened beyond age 50 years had a 6-fold higher risk of being diagnosed with cervical cancer compared with those who had an adequate negative screening history at age 50 to 64 years. That amounted to 49 cancers versus 8 cancers per 10,000 women spanning a 20-year period.
Women who were screened regularly and had a positive (abnormal) screening result between the ages of 50 years and 64 years had a risk of 86 cancers per 10,000 women over a period of 20 years. The authors note that their findings may not apply to other settings and that cervical screening methods are changing with the availability of human papillomavirus testing. Nevertheless, they say that cervical screening in women aged 50 years to 64 years has a major effect on cervical cancer rates among women aged older than 50 years. They add that the protective effect of screening at these ages weakens with time and is substantially less at 15 years after the last screen.
Reference 1. Castanon A, Landy R, Cuzick J, Sasieni P. Cervical screening at age 50-64 years and the risk of cervical cancer at age 65 years and older: populationbased case control study. PLoS Med. 2014;11:e1001585 DOI: 10.1002/cncr.28777
Content in this section does not reflect any official policy or medical opinion of the American Cancer Society or of the publisher unless otherwise noted. © American Cancer Society, 2014.
Cancer
June 1, 2014
1599
© AARON AMAT | SHUTTERSTOCK.COM
protein programmed cell death-ligand 1 (PD-L1) (carried by some cancer cells) attaches to PD-1 on T cells, they are unable to attack the cancer cells. Drugs targeting PD-1, such as the antibody therapy MK-3475, can potentially reverse that effect. In the study, researchers treated 38 patients with NSCLC with MK-3475 every 3 weeks. They found that the pretreatment PD-L1 expression level may be a good predictor of response to treatment with MK-3475. The median duration without worsening of disease among the 9 responders was at least 62 weeks.
