Vaccines committee supports Gardasil for prevention of anal cancer

The FDA’s Vaccines and Related Biological Products Advisory Committee recommended extending the indication for Merck’s human papillomavirus vaccine, Gardasil, to prevent anal cancer and anal intraepithelial neoplasia in those aged 9 to 26 years.

The recommendation will be passed along to the full FDA, but the agency is not required to follow the committee’s advice.

The FDA has approved Gardasil for both sexes as a vaccine against HPV types 6, 11, 16 and 18. These HPV types have been associated with genital warts and cervical cancer. The recommendation would extend the indication for Gardasil but would not change the indicated population.

Anal cancer represents about 4% of all lower gastrointestinal tract cancers in the US, although incidence has increased from 0.8% per 100,000 population in 1975 to 1.6% per 100,000 in 2007. Men who have sex with men (MSM) are at particular risk, but women make up 60% of patients diagnosed with anal cancer.

Merck submitted data from a double blind, placebo-controlled study in which 4,065 men were randomly assigned to Gardasil or aluminum adjuvant-containing saline as a control. The cohort included 602 MSM.

Among MSM, the point estimate of efficacy was 78% (95% CI, 40-93) for the primary composite endpoint of prevention of any grade anal intraepithelial neoplasia and anal cancer. For grade 2 or higher anal intraepithelial neoplasia, efficacy was 75% (95% CI, 9-93). There were no cases of invasive anal cancer in the study.

In the full analysis set population, efficacy was 50% (95% CI, 26-27) any grade anal intraepithelial neoplasia and anal cancer. For grade 2 or higher anal intraepithelial neoplasia, efficacy was 54% (95% CI, 18-75).

In presenting the results to the committee, Elizabeth Garner, MD, MPH, director of clinical research for Merck, said because anal cancer is the same disease in men and women, the results show that Gardasil should be indicated as a vaccine for both men and women.

“This new data shows Gardasil is efficacious against anal intraepithelial neoplasia,” Garner said “Taken together, the totality of the evidence supports an anal cancer indication for males and females.”

Most committee members concluded that Merck made a strong case for Gardasil as a vaccine for anal cancer in men. However, the study did not look at the preventive effect of Gardasil for women and not all were convinced that the company had shown conclusively that the vaccine would have a similar effect in women. Vicky Debold, PhD, RN, director of patient safety with the National Vaccine Information Center, and Pablo Sanchez, MD, professor of pediatrics at the University of Texas Southwestern Medical School, were among those who said they had concerns about extending the indication to women.

“I see the biologic possibility, but at same time, we are granting an indication when we don’t have data showing that Gardasil is preventative for women,” Sanchez said.

In the end, committee members said the data were shown to be strong enough in males to support the “logical extension” to women and girls.

“The data is very strong in males,” said Anna Durbin, MD, assistant professor in the division of disease control at the Bloomberg School of Public Health. “With what we know about anal cancer, this data also supports extending the indication for women as well.”

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