Head-to-head study of cervical cancer vaccines now under way at about 50 different sites
Phase III study has been launched for Cervarix and Gardasil
As clinicians begin to integrate use of the first cervical cancer vaccine (Gardasil, Merck & Co., Whitehouse Station, NJ) into their practice, developers of an investigational vaccine have launched a head-to-head study of the two vaccines.
The study is designed to compare the immunogenicity of Gardasil vs. Cervarix, a cervical cancer candidate vaccine under development by Glaxo-SmithKline's Rixensart, Belgium-based GSK Biologicals. The trial will compare the immune responses to human papillomavirus (HPV) types 16 and 18 in U.S. women ages 18-26, as well as evaluate the immune responses to HPV 16 and 18 in women ages 27 to 35 and 36 to 45. In addition, the study will compare immune responses to other cancer-causing HPV types.
The trial is a Phase III, randomized, observer-blind study of 1,042 U.S. women. The study is designed with two arms, with each arm stratified by three age groups, 18-26 (n = 374), 27-35 (n = 334), and 36-45 (n = 334). Some 50 sites in the United States will participate in the research, reports Jennifer Armstrong, a spokeswoman for GlaxoSmithKline. Scientists plan to issue initial study results 12 months after study enrollment is completed, with extended follow-up scheduled for another 17 months.
The company is moving forward with its search for U.S. regulatory approval. It plans to file its biologics license application with the Food and Drug Administration review by April 2007.
Is it effective?
GSK's cervical cancer candidate vaccine is targeted to prevent infection and lesions from the two most prevalent cancer-causing types of HPV: types HPV 16 and 18. It is formulated with AS04, a proprietary adjuvant system designed to sustain antibody levels over time.
GlaxoSmithKline says about 16,000 women worldwide have been vaccinated with the candidate vaccine as part of completed and ongoing clinical trials. Advanced trials of the vaccine are under way in more than 25 countries, with more than 35,000 subjects enrolled in ongoing trials, the company states. It is seeking regulatory approval in Europe, Australia, parts of Asia and parts of Latin America.
Published research indicates that the vaccine demonstrated protection up to 4.5 years against persistent infection with HPV 16 and HPV 18 and protection from pre-cancerous lesions.1 Protection also was demonstrated against infection with the third and fourth most prevalent cancer-causing types of HPV: types 45 and 31.1 More recent findings show that the cervical candidate vaccine, formulated with its proprietary adjuvant system, induced higher antibody levels and immune memory response compared to a similar HPV vaccine composition formulated with an aluminum hydroxide adjuvant.2
How will the two vaccines compare in the study? The FDA approved Gardasil, which targets HPV types 6, 11, 16 and 18, in June 2006. Gardasil also protects against vaginal and vulvar cancers, two other gynecological cancers that are linked to HPV, according to research presented in June 2006 at a meeting of the American Society of Clinical Oncology in Atlanta.3
ACS issues guidelines
The American Cancer Society (ACS) has issued guidelines calling for routine vaccination of females ages 11 to 12.4 The new guidelines join those of other major health groups, including the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians, cal-ling for immunization in this age group.
The ACS guidelines were developed by an expert panel, which reviewed existing data to create the recommendations. The panel concluded:
- Routine HPV vaccination is recommended for females ages 11 to 12.
- Females as young as age 9 may receive HPV vaccination.
- HPV vaccination also is recommended for females ages 13 to 18 years to catch up missed vaccine or complete the vaccination series.
The panel determined there is insufficient data at the present time to recommend for or against universal vaccination of females ages 19 to 26; women in this age group should discuss risk of previous HPV exposure and potential benefit from vaccination with their health care providers.4
"Ideally, the vaccine should be administered prior to potential exposure to genital HPV through sexual intercourse because the potential benefit is likely to diminish with increasing number of lifetime sexual partners," the committee members state.
Continue cancer screens
Screening for cervical cancer and precancers should continue in vaccinated and unvaccinated women, according to current ACS early detection guidelines. Why is it so important for clinicians to continue to emphasize the need for screening?
Virtually all cervical cancer is caused by HPV, says Debbie Saslow, PhD, director of the ACS's breast and gynecologic cancer division and lead author of the new guidelines. While there are more than 100 types of HPV, between 13 and 15 types are associated with cervical cancer, she explains.
Gardasil protects against two types of HPV, which together are responsible for about 70% of cervical cancer, says Saslow. Girls and women who receive this vaccine will therefore be vulnerable to the 30% of cervical cancers that are caused by other types of HPV. Also, if these females have already been sexually active when they get vaccinated, they may have already been exposed to one or both of the HPV types in the vaccine, she states. While the vaccine prevents HPV infection, it does not have any benefit if exposure already has occurred, notes Saslow. Another point of vulnerability is that some women will receive only one or two vaccine doses instead of the recommended three; these women will not receive full protection, she states.
Screening with the Pap test can detect dangerous changes in the cervix before they ever turn into cancer, or at least find cervical cancer at an early stage, when it is easier to treat. "Until we have a vaccine that prevents all or almost all types of HPV that can cause cervical cancer, women still need to get regular Pap tests and, if they are age 30 or older, they can also get the HPV test," states Saslow.
- Harper DM, Franco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: Follow-up from a randomised control trial. Lancet 2006; 367:1,247-1,255.
- Giannini SL, Hanon E, Moris P, et al. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminum salt combination (AS04) compared to aluminum salt only. Vaccine 2006; 24:5,937-5,949.
- Paavonen J for The FUTURE II Study Group. Efficacy of a quadrivalent HPV (types 6/11/16/18) L1 virus-like particle (VLP) vaccine against vaginal and vulvar pre- cancerous lesions: A combined analysis. J Clinical Oncol 2006; 24:5,011.
- Saslow D, Castle PE, Cox JT, et al. American Cancer Society Guideline for Human Papillomavirus (HPV) Vaccine Use to Prevent Cervical Cancer and its Precursors. CA Cancer J Clin 2007; 57:7-28.