Immunotherapeutic agents for cervical cancer include vaccines to prevent infection with oncogenic strains of HPV and monoclonal antibody treatment for advanced or metastatic disease.
Approved immunotherapeutic agents
Combination therapy/treatment algorithms
Approved immunotherapeutic agents (for cervical cancer)
Gardasil (Merck), a vaccine that greatly reduces the risk of infection with high-risk HPV was approved in 2006 for the prevention of cervical cancers (and other cancers associated with HPV infection, including vulvar, vaginal and anal cancers). In 2009, an additional HPV vaccine, Cervarix (GlaxoSmithKline), was approved. Gardasil and Cervarix guard against infection with two high-risk strains, 16 and 18, that are responsible for approximately 70% of cervical cancers; Gardasil also protects against infection with types 6 and 11, which are associated with most cases of genital warts. Gardasil 9 was approved in 2015 and prevents against the same strains as Gardasil in addition to five other high-risk strains: 31, 33, 45, 52 and 58.
Gardasil is approved for the prevention of HPV-associated cancers, precancerous lesions and genital warts in males and females ages 9 to 26 years; Gardasil 9 is approved for females ages 9 to 26 years and males ages 9 to 15 years; and Cervarix is approved for females ages 9 to 25 years. In clinical trials, these vaccines were 97% to 100% effective at preventing infection with the indicated types of HPV. Although these vaccines prevent infection with certain strains of high-risk HPV, they do not treat cancer in patients who have already been infected with the virus.
All three vaccines are given in three intramuscular doses over the course of 6 months; for both males and females vaccinated using Gardasil 9 between the ages of 9 and 14 years, only 2 doses are required, with the second dose administered between 6 and 12 months of the first.
Bevacizumab was approved in 2014 for first- or second-line therapy in patients with recurrent or metastatic cervical cancer that has failed to respond to other treatment protocols.
Cervical cancer combination therapy/treatment algorithms
The Advisory Committee on Immunization Practices makes the following recommendations for the dosing and administration of HPV vaccines:
- Vaccination should be initiated at 11 to 12 years of age, though it may be initiated as young as age 9.
- Females ages 13 to 26 years and males ages 13 to 21 years who have not been previously vaccinated or have not completed the three-dose series should be vaccinated.
- Men who have sex with men, and immunocompromised individuals who have not been previously vaccinated, may be vaccinated through the age of 26.
- If a patient has already received a vaccination dose and the type of vaccination (Gardasil, Gardasil 9 or Cervarix) is unknown, or if the provider wishes to switch to Gardasil 9 for the completion of the vaccination series, any of the three vaccines may be used to complete the series for females, while Gardasil or Gardasil 9 should be used for males.
For the first-line treatment of recurrent or metastatic cervical cancer, the NCI recommends the following agents:
- Cisplatin, paclitaxel and bevacizumab;
- Cisplatin and paclitaxel;
- Topotecan, paclitaxel and bevacizumab; or
- Carboplatin and paclitaxel.
Current clinical trials for cervical cancer
Several monoclonal antibodies are being investigated for the treatment of cervical cancer, including pembrolizumab, nivolumab, ipilimumab and durvalumab in combination with tremelimumab. Other investigative agents include several peptide vaccines and two antibody-drug conjugates, tisotumab vedotin (Genmab) and sacituzumab govitecan (Immunomedics).