Ana Oaknin, MD

As reported in The Lancet Oncology by Ana Oaknin, MD, of the Medical Oncology Service at Vall d´Hebron Institute of Oncology, Vall d´Hebron Barcelona Hospital, and colleagues, the phase I/II CheckMate 358 trial showed that both nivolumab monotherapy and nivolumab/ipilimumab regimens were active in patients with recurrent or metastatic cervical squamous cell carcinoma.

In the open-label trial, 176 previously treated or untreated patients from sites in 10 countries were enrolled between October 2015 and March 2020. Patients were categorized as follows:

• Enrolled into a nivolumab monotherapy group receiving 240 mg every 2 weeks (n = 19)
• Randomly assigned to nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks (NIVO3 plus IPI1 group; n = 45) or nivolumab at 1 mg/kg every 3 weeks plus ipilimumab at 3 mg/kg every 3 weeks for four cycles, then nivolumab at 240 mg every 2 weeks (NIVO1 plus IPI3 group; n = 45)
• Enrolled in a NIVO1 plus IPI3 expansion group (n = 67; pooled NIVO1 plus IPI3 group = 112 patients).

Treatment continued until disease progression, unacceptable toxicity, or for up to 24 months. The primary endpoint was investigator-assessed objective response rate.

Responses

In the nivolumab monotherapy group, an objective response was observed in 5 of 19 patients (26%, 95% confidence interval [CI] = 9%–51%), with a complete response in 4 (21%). Median response duration was not reached (95% CI = 35.3 months to not reached). Median progression-free survival was 5.1 months, and median overall survival was 21.6 months.

In the NIVO3 plus IPI1 group, an objective response was observed in 14 of 45 patients (31%, 95% CI = 18%–47%), with a complete response in 3 (7%). Median response duration was 24.4 months (95% CI = 8.7 months to not reached). Median progression-free survival was 3.8 months, and median overall survival was 15.2 months.

In the randomized NIVO1 plus IPI3 group, objective response was observed in 18 of 45 patients (40%, 95% CI =26%–56%), with a complete response in 5 (11%). Median response duration was 34.1 months (95% CI = 15.3 months to not reached). Median progression-free survival was 7.2 months, and median overall survival was 24.7 months.

In the pooled NIVO1 plus IPI3 groups, an objective response was observed in 43 of 112 patients (38%, 95% CI = 29%–48%), with a complete response in 8 (7%). Median response duration was 34.1 months (95% CI = 11.5 months to not reached). Median progression-free survival was 5.8 months, and median overall survival was 20.9 months.

Adverse Events

The most common grade 3 or 4 treatment-related adverse events were diarrhea, hepatic cytolysis, hyponatremia, pneumonitis, and syncope in one patient (5%) each in the nivolumab group; diarrhea, increased gamma-glutamyl transferase, increased lipase, and vomiting in two patients (4%) each in the NIVO3 plus IPI1 group; and increased lipase in nine patients (8%) and anemia in seven patients (6%) in the pooled NIVO1 plus IPI3 group. Serious treatment-related adverse events occurred in 16%, 27%, and 42% of patients, respectively. One treatment-related death, from immune-mediated colitis, was observed in the pooled NIVO1 plus IPI3 group.

The investigators concluded: “Nivolumab monotherapy and nivolumab plus ipilimumab combination therapy showed promise in the CheckMate 358 study as potential treatment options for recurrent or metastatic cervical cancer. Future randomized controlled trials of nivolumab plus ipilimumab or other dual immunotherapy regimens are warranted to confirm treatment benefit in this patient population.”

Dr. Oaknin is the corresponding author of The Lancet Oncology article.

Disclosure: The study was funded by Bristol Myers Squibb and Ono Pharmaceutical. For full disclosures of the study authors, visit thelancet.com.