Sharad Ghamande, MD
Vaccine therapy is useful in both the prevention and treatment of cervical cancer, explains Sharad Ghamande, MD, and phase II findings of such treatment have demonstrated a survival benefit in a pretreated population.
In the phase II GOG/NRG-0265 study, treatment with axalimogene filolisbac (AXAL), an immunotherapy targeting human papillomavirus (HPV)-infected cells, led to an unprecedented 1-year survival rate in patients with recurrent, metastatic cervical cancer. AXAL induces antitumor T-cell immunity and breaks immune tolerance in the tumor microenvironment.
Results showed that patients had a median overall survival (OS) of 6.2 months and a 12-month survival of 38%. Disease control was achieved in 32% of patients based on investigator assessment of best response of the 50 evaluable patients treated with AXAL, 26 had received 2 or more lines prior lines of therapy.
Based on this activity, AXAL is now being investigated in the global phase III AIM2CERV trial as adjuvant monotherapy to prevent recurrence in patients with high-risk cervical cancer treated with chemoradiation (NCT02853604).
In an interview with OncLive
, Ghamande, associate professor, Georgia Cancer Center, Augusta University, discussed the findings from GOG/NRG-0265, as well as the impact of vaccines for patients with cervical cancer.
OncLive: What was the rationale of the phase II GOG/NRG-0265 study for patients with cervical cancer?
: In the United States, there are 13,000 newly diagnosed cases of cervical cancer every year and about 4000 patients die. However, worldwide, there are almost 400,000 new cases of cervical cancer diagnosed every year. Unfortunately, almost 80% of patients present with advanced disease. In any given year, there are 250,000 women who die of cervical cancer.
Overall, there are 2.3 million women with active cervical cancer in the world. These are staggering numbers. We have not made as much progress as we should have when treating cervical cancer. We are doing better with prevention, with Pap smears and the evolution of liquid-based cytology and HPV vaccines. We are at a point where we can make a tremendous impact with vaccinations that are proven to prevent against cervical cancer. However, in many parts of the world, particularly the developing world, vaccines are still not as prevalent.
What are the most pressing unmet needs in cervical cancer?
We need to do a better job at preventing the disease. Shockingly, it is one of the few cancers that can be prevented and, yet, we do a poor job.
The second unmet need is that 80% of cervical cancer is advanced at presentation. If a patient has early cervical cancer, they tend to do quite well. However, with advanced cervical cancer, the survival rates are not great. Many of these patients will recur after standard radiation and chemotherapy. Once cervical cancer recurs it is almost always a lethal disease, which makes the treatment of patients with recurrent cervical cancer an unmet need.
What was the design of GOG/NRG-0265?
GOG/NRG-0265 was a very interesting phase II trial using a novel immunotherapy approach for patients who had recurred and had gone through 1 line of chemotherapy. If you look at the last 30 to 40 years of cervical cancer in the United States, there have only been 3 FDA-approved drugs, which is staggering compared with breast cancer where there are 60 FDA-approved drugs. The last FDA approval was with chemotherapy and bevacizumab (Avastin). However, we are still far behind. Immunotherapy is a very exciting wave of research to help this unmet need.
GOG/NRG-0265 is an immunotherapy trial using a compound called AXAL, where the HPV-16 E7 protein is combined with Listeria monocytogenes. This combination is given intravenously as a vaccine. Once the vaccine is administered, it causes a tremendous HPV-specific T-cell response that attacks the cancer cells. This is important because cervical cancer is almost all caused by HPV, making this a unique and robust way of targeting the disease.
This compound makes the tumor microenvironment better by downregulating inhibition molecules like T-regulatory cells. This is a robust combination because it has multiple ways to attack. There are no new antibodies because most of the Listeria is taken up inside the cell.
This trial investigated patients who had failed 1 line of chemotherapy in the recurrent setting. The patients received the vaccine in the first stage of the trial once a month for 3 doses. Patients could stay on the vaccine as long as they did not progress or have too many toxicities.