Patients with recurrent or metastatic cervical cancer were treated with combination Opdivo and Yervoy in the CheckMate-358 clinical trial.
Patients with recurrent or metastatic cervical cancer may have new hope in an immunotherapy combination currently being examined in clinical trial.
In the CheckMate-358 study, researchers are looking at how tumors react to the treatment combination of Opdivo (nivolumab) and Yervoy (ipilimumab), both immune checkpoint inhibitors, regardless of tumor PD-L1 expression.
PD-L1 is a protein that is found on normal cells and some cancer cells but when it binds to another protein, PD-1, it keeps T cells from killing the cancer cells. Immune checkpoint inhibitors work to bind PD-L1 and block its binding to PD-1 in hope to kill the cancer.
The trial, which is still enrolling patients, included 91 participants with confirmed squamous cell carcinoma of the cervix and who received two or fewer prior systemic therapies for their disease. They were randomly selected to receive one of two different regimens: a higher dose of Opdivo plus Yervoy or a lower dose of Opdivo plus a higher dose of Yervoy, then followed by another dose of Opdivo.
Most patients had metastatic disease and more than 80% in each group had received prior platinum therapy and radiation therapy. More than 60% of patients in each group had PD-L1 expression greater than or equal to 1%.
Imaging was conducted every eight weeks for a year and then every 12 weeks. Patients continued treatment until disease progression, side effects occurred or they had been on it for a maximum of two years.
Researchers found that the combination worked better in patients who didn’t receive prior therapy compared with those who did.
“Very provocatively, across both regimens, efficacy was better in patients without prior systemic therapy,” Dr. Ana Oaknin, from Vall d’Hebron University Hospital in Barcelona, Spain, said during the 2019 European Society for Medical Oncology (ESMO) Congress. “Additionally, responses were durable; at a median follow-up of more than 10 months, the median duration of response was not reached for either regimen in patients without prior systemic therapy.”
Among those treated with the higher dose of Opdivo in combination with Yervoy, patients who were previously untreated experienced a median progression-free survival, or the time from treatment to disease progression or worsening, of 13.8 months, compared with 3.6 months in those previously treated at 10.7 months of follow-up.
At 13.9 months of follow-up, those treated with the higher dose of Yervoy plus Opdivo demonstrated a median progression-free survival of 8.5. months for patients with no prior systemic therapy, compared with 5.8 months in those previously treated.
Median overall survival was not reached in the higher dose Opdivo group for patients with no prior therapy. But it was 10.3 months for those who were previously treated for recurrent or metastatic disease.
Four patients in each group had a complete response to treatment, and eight patients in the higher dose Opdivo group and 15 in the higher dose Yervoy group had partial responses.
The researchers saw a higher incidence of treatment-related side effects and serious side effects in the higher dose Yervoy group, which led to treatment discontinuation.
Patients with recurrent or metastatic cervical cancer who have not had prior therapy are currently treated with a combination of cisplatin, paclitaxel and Avastin (bevacizumab). However, median overall survival with this combination is less than 17 months.
“Unfortunately, for those patients who progress on chemotherapy and bevacizumab, treatment options are very limited,” said Oaknin, adding that with the data of CheckMate-358, there is strong clinical interest and it warrants further investigation in this patient population.