ILCN recently interviewed William K. Evans, MD, FRCPC, professor emeritus of oncology at McMaster University, Hamilton, Ontario, Canada, who chairs the IASLC Tobacco Control and Smoking Cessation Committee. The committee’s mission is to improve patient care by raising awareness of cessation-related data and by provision of information regarding the latest and most successful cessation techniques for patients with lung cancer.
Learn more about recent developments and research in tobacco control and cessation from Dr. Evans in the following Q&A.
ILCN: Three years ago during Lung Cancer Awareness Month, IASLC issued a policy statement discouraging the use of electronic cigarettes. The American Association for Cancer Research and the American Society for Clinical Oncology also recently released a joint policy statement with recommendations for regulating electronic nicotine delivery systems (ENDS) to protect public health. Such statements support efforts to effect policy change. What do you see as the top regulatory or legislative goal or goals regarding ENDS products? And what next steps should IASLC and other organizations take to move toward those goals?
Dr. Evans: It is commendable that AACR and ASCO have jointly called attention to the alarming increase in the use of electronic nicotine delivery systems (ENDS). Initially ENDS were proposed as smoking cessation aids as the aerosol produced by these devices does not contain the high concentrations of toxins and carcinogens contained in tobacco smoke. However, considering how these devices are being marketed and used, they might be more accurately referred to as electronic nicotine addiction devices.
It should be apparent to everyone that the aggressive marketing of these devices to youth is responsible for the increasing numbers of youth and adults who are addicted to their use as well as for many transitioning to tobacco. There can be no justification for the marketing of a product that addicts individuals, particularly young people, to nicotine and contaminates their lungs with potentially dangerous substances, including carcinogens, no matter the quantity of hazardous materials.
The legislative and regulatory recommendations from AACR-ASCO are thoughtful and sound, although calling for a ban only on non-tobacco-flavored ENDS products that contain natural or synthetic nicotine falls short of what is really needed. The IASLC and other health organizations should strongly support efforts by regulatory agencies to end the sale of ENDS unless manufacturers can demonstrate a health benefit. If used as a smoking cessation aid—despite the relatively weak evidence of benefit—ENDS should ideally be prescribed by a licensed medical practitioner when a patient enters a smoking cessation program and has previously failed the current evidence-based first-line approaches to smoking cessation.
ILCN: Speaking of regulatory goals, the US Food and Drug Administration recently proposed prohibiting the sale of menthol cigarettes and flavored cigars to reduce tobacco-related disease and death. The FDA said in its proposal it believed the move would reduce the number of young people who take up smoking because flavors increase appeal and make cigars easier to use. While not a total prohibition of tobacco, is this a step in the right direction? Does evidence suggest such a change would reduce the number of adolescents who take up smoking?
Dr. Evans: Many countries have banned flavors and menthol already and it would be an important and beneficial step for the FDA to move forward with its proposed plan to prohibit the sale of menthol cigarettes and flavored (including menthol) cigars. These products are appealing to youth and facilitate young people becoming regular—i.e., addicted—tobacco users. Menthol is more soothing to the oral and airway mucosa than non-menthol tobacco smoke. Menthol cigarettes also have a greater appeal in the Black population—very much driven by tobacco industry targeted advertising. 1
There is little doubt that prohibiting the sale of menthol cigarettes and flavored cigars would have an impact on combusted product consumption. Legislation has been passed in other countries with positive results. Canada banned menthol cigarettes in 2015 and pre- and post-cohort studies conducted in seven of Canada’s provinces provide precise estimates of the impact of the menthol ban on quitting. In an article in Tobacco Control,2 Canadian estimates of the impact of the menthol ban were applied to the US population. After the menthol cigarette ban in Canada daily menthol cigarette users were more likely than non-menthol users to have quit smoking (difference = 8.0%; 95% CI: 2.4% to 13.7%, p = 0.005). The projected number of people who smoke who would quit after a US menthol ban was estimated to be 789,724 daily users, including almost 200,000 Black Americans.2
ILCN: In other youth smoking prevention news, a recent study in JAMA Network Open looked at the impact of vaping prevention advertising on adolescents. The study’s authors concluded that their findings suggest vaping prevention ads reduced the susceptibility of youth to vaping. Does this new data align with previous efforts to identify effective methods for preventing addictive substance use in adolescents? Additionally, are you aware of any large-scale efforts to prevent smoking and vaping in youth? And are such efforts seeing success?
Dr. Evans: It has been known for decades that public health education—including prevention advertising—works. The media educational program at the FDA’s Center for Tobacco Products is one of their major offices. Its prevention programs are strenuously evidence-based and tested in the intended audience before release. Subsequently, there is follow-up research to demonstrate that the ads ‘worked’ and did not have unintended consequences. The study by Noar et al.3 was a three-group randomized clinical trial of US adolescents aged 13 to 17 who were susceptible to or were current e-cigarette users. They were randomized to vaping prevention trial groups (health harms or addiction themed advertisements) from the FDA’s Real Cost campaign or a control group, which was exposed to neutral videos about vaping. The findings suggested that the vaping prevention advertisements from the FDA Real Cost campaign led to lower susceptibility to vaping by adolescents and that there was a spillover effect of the vaping messages on cigarette smoking outcomes. Thus, the JAMA paper adds evidence to support what has been known.
A study by Noel Brewer et al4 looked at the impact of e-cigarette health warnings on the motivation to vape or smoke cigarettes. The study was undertaken because of the prevailing view that health warnings about electronic cigarettes would drive people away from vaping towards smoking cigarettes.
This study of 2,218 US adults who used e-cigarettes, tobacco cigarettes, or both randomized participants to one of three warning types: controlled text about littering, text-only e-cigarette warning, or pictorial e-cigarette warning. Participants were also randomized to viewing one of three e-cigarette warning topics—a message about nicotine addiction, a message about the health hazards of use, or both nicotine addiction and health hazards.
The text warnings lead to higher intentions to quit vaping than controls and pictorial warnings lead to still higher intentions to quit vaping than text. In addition, text warnings about health hazards elicited higher intentions to quit vaping than nicotine addiction warnings. The authors suggest that health warnings may motivate users to quit vaping and discourage smoking and that the most promising warnings are those that had imagery and include health hazards other than nicotine addiction.
Against the evidence from this and numerous other studies, it is notable that the US has yet to implement graphic health warnings on cigarette packages, again, unlike most other countries.
ILCN: Switching gears from prevention to cessation, according to an article published in the Journal of Thoracic Oncology earlier this year, cytisine therapy is a useful treatment option for smoking cessation—specifically as part of a lung cancer screening program. While cytisine has been in use for many years in some parts of the world, its low cost—and minimal profit potential—may make wider adoption unlikely. Do you see potential for increased use of cytisine in the smoking cessation toolbox? Are there other investigations of potential smoking cessation aids that readers may find interesting?
Dr. Evans: Cytisine is a plant-based alkaloid that binds with high affinity to the α4 β2 nicotinic acetylcholine receptor, which is responsible for the central effects of nicotine. This natural product inspired the development of varenicline (as a new chemical entity that could be patented), and it can reduce the craving to smoke during the pre-quit period and the withdrawal discomfort of quitting.
Cytisine has been demonstrated to be an effective smoking cessation aid in multiple studies. A systematic review and meta-analysis of eight randomized controlled trials of 4,020 users of tobacco reported a 59% (p<0.00001) higher abstinence rate from smoking while taking cytisine versus placebo.5 An open label randomized trial comparing cytisine to nicotine replacement therapy (NRT) in people who smoked every day showed a self-reported cessation rate at one month of 40% in those taking cytisine versus 31% for NRT. The 6-month self-reported cessation rate was also higher with cytisine (22% vs 15%).6
A randomized clinical trial, undertaken in 1,452 Australian adults who smoked every day, compared a 25-day course of cytisine to a standard 84-day course of varenicline to determine if cytisine was at least as effective as varenicline.7 The 6 months continuous abstinence confirmed by carbon monoxide testing was 12% in the cytisine group and 13% in the varenicline group. Self-reported adverse events were reported less frequently in the cytisine group.
Cytisine has so far been inexpensive and has been used for decades in eastern Europe and Russia. Canada approved it for cessation in 2017 as a natural health product making it available without prescription from select pharmacies, health shops, and directly online from the manufacturer. It costs about $56 for a 25-day treatment course compared to NRT ($360-$449), bupropion ($215), and varenicline ($340) in Canada.8 However, most of the world does not have access to the product.
Achieve Life Sciences has been conducting studies of cytisinicline (another name for cytisine) to obtain FDA approval and there are numerous other trials ongoing in the US and elsewhere in the world to assess the effectiveness of cytisine either in comparison to standard smoking cessation approaches or in combination with current best interventions. One can only hope that the US FDA does not require the product to be a prescription drug, as that would dramatically decrease its usefulness for public health.
In addition, we can hope that Achieve makes the product available as an inexpensive drug to help people quit, as many who continue to smoke in developed countries are from marginalized communities, have lower socioeconomic status, and lower educational attainment, and hence have fewer resources to purchase an expensive smoking cessation aid.
ILCN: Can you give us an update from the IASLC Tobacco Control and Smoking Cessation Committee (TCSC)? What has the committee been working on? What should IASLC members know if they’re interested in joining the committee?
Dr. Evans: The Tobacco Control and Smoking Cessation committee is organized into several working groups. The role of the Education working group is to develop content for the annual World Conference on Lung Cancer, as well to develop strategies and materials to inform and enable oncologists, as well as primary care providers globally with the tools to combat the tobacco use epidemic. The Collaborations working group is seeking opportunities to work with other organizations and institutions that are also engaged in tobacco control and smoking cessation initiatives. Through the Engagement working group, the committee is reaching out to low- and middle-income countries to help them as they struggle to defend themselves against the tobacco industry’s efforts to addict their populations.
The Research working group is developing an agenda of research activities and potential collaborations with other IASLC committees. There is considerable interest in working with the staging committee as it revises the staging system for lung cancer and to integrate smoking status into the staging system.
The TCSC is also promoting awareness of the IASLC position statement on smoking after a cancer diagnosis. The position statement is being distributed through IASLC CEO Karen Kelly, MD, to leading cancer organizations identified by members of the TCSC. These organizations are encouraged to inform their members about the IASLC position statement and to endorse it on their websites.
References
- 1. Delnevo CD, Ganz O, Goodwin RD. Banning menthol cigarettes: A social Justice issue long overdue. Nicotine Tob Res 2020 Oct; 22(10): 1673-1675.
- 2. Fong GT, Chung-Hall J, Meng G, et al. Impact of Canada’s menthol cigarette ban on quitting among menthol smokers: pooled analysis of pre-post evaluation from the ITC Project and the Ontario Menthol Ban Study and projections of impact in the USA [published online ahead of print, 2022 Apr 28]. Tob Control. 2022; tobaccocontrol-2021-057227. doi:10.1136/tobaccocontrol-2021-057227
- 3. Noar SM, Gottfredson NC, Kieu T, et al. Impact of Vaping Prevention Advertisements on US Adolescents: A Randomized Clinical Trial. JAMA Netw Open. 2022;5(10):e2236370. doi:10.1001/jamanetworkopen.2022.36370
- 4. Brewer NT, Chapman GB, Gibbons FX, Gerrard M, McCaul KD, Weinstein ND. Meta-analysis of the relationship between risk perception and health behavior: the example of vaccination. Health Psychol. 2007;26(2):136-145. doi:10.1037/0278-6133.26.2.136
- 5. Hajek P, McRobbie, Myers K et al. Efficacy of cytisine in helping smokers quit: systematic review and meta-analysis. Thorax 2013; 68: 10370-1042.
- 6. Walker N, Howe C Glover M et al. Cystine versus nicotine for smoking cessation/ N Engl J Med 2014; 371: 2353-2362.
- 7. Courtney RJ, McRobbie H, Tutka P et al. Effect of cytisine vs varenicline on smoking cessation: a randomized clinical trial. JAMA 2021 Jul 6; 326(1): 56-64.
- 8. Karnieg T, Wang X Cytisine for smoking cessation. CMAJ 2018 May 14;190: E596. Doi: 10.1503.cmaj.171371.