HPV Vaccine Gets High Marks in Trial
|
|
An investigational vaccine aimed at cervical cancer has proved 100% effective against cervical pre-malignant lesions associated with the most prevalent strains of the human papilloma virus (HPV), according to researchers here.
Results of the Phase III study of Merck’s quadrivalent recombinant vaccine, known as Gardisil, are to be presented Friday at the Infectious Diseases Society of America meeting here.
In the FUTURE II trial, an international multicenter study, the vaccine protected all 5,301 women who had no study protocol violations for receiving the shots and who were followed for an average of 17 months.
By comparison, 21 cases of pre-cancerous lesions were detected in 5,258 women given a placebo vaccine. The vaccine, which protected against HPV strains 16 and 18, is given three times: day one, month two, and month six.
The difference in protection was statistically significant at the p<.001 level, said Laura Koutsky, Ph.D., the study’s principal investigator, a professor of epidemiology at the University of Washington in Seattle.
“These are the first pivotal data to show that vaccination with Gardasil reduced HPV-16 and 18-related cervical pre-cancer and non-invasive cervical cancer,” she said.
Merck is expected to file for FDA approval of the vaccine in December.
In addition, the researchers followed women who might have missed some of the vaccinations. The results showed that of 5,736 women who received at least some of the inoculations, there was only one case of high-grade pre-malignancy or non-invasive cancer, a 97% reduction. This contrasted with 36 such cases among women in the placebo arm of the trial.
No one dropped out because of serious vaccine-related adverse events. Adverse events were higher among those who received Gardasil compared with placebo recipients, the most common being injection site reactions, Dr. Koutsky said.
Approximately 20 million American men and women are infected with HPV, and HPV types 16 and 18 are responsible for about 70% of all cervical cancer cases. HPV types 6 and 11, also included in the quadrivalent vaccine, are responsible for 90% of cases of genital warts.
Overall, the FUTURE II trial enrolled more than 12,000 women in 13 countries. Participants were 16 to 26 years of age. The study evaluated the prevalence of cervical intraepithelial neoplasia (CIN) Grade 2/3. Grade 2 is a moderate-grade lesion; Grade 3 includes high-grade lesions and carcinoma in situ. It also evaluated the rate of adenocarcinoma in situ. CIN 3 and AIS are both defined as stage 0 cancer by the International Federation of Gynecology and Obstetrics.
“This is the real deal,” said Richard Whitley, MD, professor of pediatrics, microbiology, medicine and neurosurgery at the University of Alabama at Birmingham. “The data presented by Merck is the most remarkable vaccine study I have ever seen in my life. This is a significant breakthrough.”
Dr. Whitley said he reviewed the data and is convinced that the scientific performance of the study is accurate and that the finding of 100% protection is accurate.
“However,” he said, “this is not a real world setting. These women were carefully screened and followed in this study. We don’t know what the results will be when we start inoculating larger numbers of women and follow them for longer periods of time.”
The women in the study were all free of HPV infection when the trial began. Dr. Whitley said further studies will have to determine whether the vaccine is therapeutic—that is will it protect women who are already infected from undergoing transformation that results in cancer.
He also said the data do not deal with older women in their 30s and 40s or younger girls. “We also don’t know whether there will be booster shots required to maintain protection,” he said.
Dr. Whitley said that he expects the FDA will require extensive Phase IV postmarketing studies that may answer a number of those questions.
Print Version
Tell-a-Friend comments powered by Disqus
