In the past, cervical cancer killed more women than any other cancer, but this has changed with the development of new tests that have helped to diagnose it early and reduce mortality. About 14,480 new cases of invasive cervical cancer will be diagnosed in 2021 in the United States, and about 4,290 women will die from this cancer this year.
Cervical cancer is divided into several subtypes. Squamous-cell carcinoma is the most common (90%) type of cervical cancer. Adenocarcinoma is the second main type of cervical cancer.
The treatment options available for patients diagnosed with advanced cervical cancer are still limited. Currently, the PD-1 inhibitor Keytruda (pembrolizumab) is the only immunotherapy that is approved by the FDA for the treatment of patients with advanced cervical cancer, but only for patients whose tumors express the PD-1 protein, which is found on some cancer cells and promotes cancer growth and progression.
Currently, no immunotherapy has been approved for patients with advanced cervical cancer whose tumor does not express the PD-1 or PD-L1 protein.
At the 2021 ASCO Annual Meeting, the results of a recent phase 2 clinical trial that is investigating balstilimab, a new immunotherapy and a new PD-1 inhibitor, that has not yet been approved by the FDA, in patients with recurrent (coming back) or metastatic (spreading to other organs) cervical cancer, were presented by Cailin E. Joyce, MD, from Agenus company, which manufactures this new immunotherapy.
New Results in Advanced or Metastatic Disease
Balstilimab was investigated as monotherapy (the only treatment) in a phase 2 clinical trial of 140 patients with recurrent or metastatic cervical cancer that had relapsed (returned) after they received platinum-based chemotherapy for advanced cervical cancer.
The results showed that overall, 17.6% of patients with metastatic cervical cancer who received balstilimab responded to treatment, regardless of their PD-1/PD-L1 status, and the average length of the response was 15.4 months, a significant extension of survival for this patient population.
In patients with squamous-cell carcinoma, the response rate was 17.6%, which increased to 21.0% in patients with squamous-cell carcinoma who had PD-L1 expression. In patients with adenocarcinoma, the second main type of cervical cancer, the response rate was 12.5%, which increased to 20.0% in those with adenocarcinoma associated with PD-L1 expression.
The average duration of response was 15.4 months in patients with squamous-cell carcinoma and 8.5 months in the patients with adenocarcinoma. In patients with PD-L1 and squamous-cell carcinoma, the average duration of response was not reached (meaning patients are still responding to therapy) and was 7.1 months in those with adenocarcinoma.
“In the phase 2 study, balstilimab exhibited higher overall response rates and duration of responses than those reported for other PD-1 antibodies,” said Dr. Joyce. “Notably, balstilimab exhibited durable responses even in patients with poorest prognosis due to PD-L1-negative status or adenocarcinoma histology.”
These study results support the clinical findings from earlier studies, according to Dr. Joyce. As expected, balstilimab enhanced the T-cell killing of cancer cells that express PD-1 and PD-L1, which resulted in improved outcomes for patients with this protein.
But these results also show that balstilimab is a promising new therapy for patients with recurrent or metastatic cervical cancer, regardless of whether their tumor expresses the PD-1 or PD-L1 protein.
“These data indicate the potential activity of balstilimab, regardless of PD-L1 status,” Dr. Joyce said. “In summary, our results demonstrate the potential for differentiated activity of balstilimab in the clinic,” she concluded.
FDA Approval Pending
In 2020, the FDA granted balstilimab a fast-track review for the treatment of patients with cervical cancer, as well as for use in combination with a different type of immunotherapy, zalifrelimab, a new CTLA-4 inhibitor, for patients with relapsed or refractory cervical cancer.
The combination of balstilimab plus zalifrelimab has shown a superior overall response rate and longer duration of response compared with balstilimab alone.
And in April 2021, based on these new study results, a new application was submitted to the FDA for balstilimab, for the treatment of patients with recurrent or metastatic cervical cancer. The FDA is expected to issue its final decision regarding the use of balstilimab for the treatment of patients with recurrent or metastatic cervical cancer in December 2021.
These are promising developments for all patients with advanced cervical cancer, including patients whose tumor does or does not express the PD-1 protein.
Key Points
- The treatment options available for patients diagnosed with advanced cervical cancer are still limited
- Currently, the PD-1 inhibitor Keytruda is the only immunotherapy approved by the FDA for patients with advanced cervical cancer whose tumors express the PD-1 protein
- Balstilimab is a new PD-1 inhibitor that is being investigated for the treatment of patients with recurrent or metastatic cervical cancer
- Results of a new study showed that 17.6% of patients with metastatic cervical cancer who received balstilimab responded to treatment, regardless of their PD-1 status
- In patients with squamous-cell carcinoma, the most common type, the response rate was 17.6%, which increased to 21.0% in patients with PD-L1 expression
