CHICAGO – The 9-valent human papillomavirus (HPV) vaccine recently approved by the Food and Drug Administration has high efficacy for preventing disease caused by the vaccine-covered viral types and is well tolerated, according to end-of study data from a randomized trial.
The vaccine was on par with the quadrivalent vaccine when it came to protection against infection with the four original viral types covered by both vaccines. Additionally, for the five new viral types, it was associated with a 97% reduction in all cervical, vaginal, and vulvar intraepithelial neoplasia, a 100% reduction in cervical intraepithelial neoplasia 3, and a more than 90% reduction in related procedures and treatments, investigators reported at the Annual meeting of Society of Gynecologic Oncology. Meanwhile, it had a good safety profile.
Susan London/Frontline Medical News
Dr. Elmar A. Joura
“The consistency of the data is very reassuring,” said Dr. Elmar A. Joura of the Medical University of Vienna, General Hospital, and Comprehensive Cancer Center, also in Vienna.
Dr. Marcela delCarmen, session comoderator and a gynecologic oncologist at the Massachusetts General Hospital in Boston, asked, “You’ve presented data on the efficacy of the vaccine in the study population, but do you have any data on the effectiveness or the impact that the vaccine will have on the public health atmosphere of the general population?”
“First of all, we saw that the vaccine was doing exactly what was expected. These vaccines don’t have any therapeutic effect, so those women who have been infected at the time of vaccination, we did not observe a benefit during the course of the study. But from the previous study of the quadrivalent vaccine, we know [that] over the course of time, they also will get some benefit,” Dr. Joura replied.
“The second thing is, the vaccine really has the potential with this high effectiveness to change the screening practice in the long term. But what’s definitely needed is good coverage. And in many countries and also in this country, the coverage rates are far from optimal. Once you achieve a rate like in Australia or the United Kingdom, then the next step definitely is a change of screening algorithm,” such as a switch to primary HPV screening, he added.
There is a persistent medical need to develop new HPV vaccines, even though two highly effective vaccines have been on the market for some time, Dr. Joura maintained. “With HPV 16 and 18, you cover about 70% of invasive cervical cancer and about 50% of cervical precancer. Adding the next five most common most oncogenic HPV strains would give a coverage of 90% for both invasive and precancer, giving an additional benefit of 20% for invasive cancer and 35% for cervical precancer,” he elaborated.
In the Merck-sponsored phase IIb/III trial, the investigators randomized 14,215 women aged 16-26 to double-blind receipt of the quadrivalent vaccine (Gardasil, which covers viral types 6, 11, 16, and 18) or the 9-valent vaccine (Gardasil 9, which additionally covers viral types 31, 33, 45, 52, and 58). “It was not possible to have this trial placebo-controlled since two effective vaccines were available, so the controls were vaccinated with the quadrivalent HPV vaccine,” Dr. Joura explained. The women had follow-up with sample collection for up to 54 months.
Initial results showed that antibody titers for the original four viral types in the group given the 9-valent vaccine were noninferior to those in the group given the quadrivalent vaccine, and when compared against the historical placebo arm of the quadrivalent vaccine trial, there was dramatic and near full protection against type 16- and 18-related cervical, vaginal, and vulvar neoplasia. These findings led to approval of the vaccine late last year and a recent publication (N. Engl. J. Med. 2015;372:711-23).
The new, end-of-study data, capturing roughly an additional year of observation, showed that relative to the quadrivalent vaccine, the 9-valent vaccine provided good protection for the five new viral types among women negative for these types at baseline: Efficacy was 97.7% for protection against any neoplasia of the cervix, vagina, or vulva; 97.4% for protection against high-grade neoplasia; and 96.0% for protection against 6-month persistent infection.
“What is important for public health decisions is what is the effect on procedures and treatments,” Dr. Joura said. In fact, the 9-valent vaccine was highly efficacious for reducing external genital biopsies (92.3% risk reduction), cervical biopsy (97.7%), and loop electrosurgical excision procedure/conization (90.2%) related to the five new viral types covered.
The rate of vaccine-related adverse events was 92.2% with the 9-valent vaccine and 87.6% with the quadrivalent vaccine, with the difference mainly due to more injection site reactions with the former. There was two vaccine-related serious adverse events in the 9-valent group and one in the quadrivalent group.