Nivolumab ± Ipilimumab Yields Durable Responses in Cervical Cancer

"Long-term data for the nivolumab monotherapy group show that this agent continues to be a viable treatment option in the second-line or later-line setting for patients with recurrent or metastatic cervical cancer," according to the study authors.

Nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) showed promise for patients with recurrent or metastatic cervical cancer, according to results from the phase 1/2 Checkmate 358 trial (NCT02488759).

Three patient cohorts were assessed for this trial. Nivolumab monotherapy was given at 240 mg every 2 weeks; the 2 combination cohorts included nivolumab at 3 mg/kg (NIVO3) every 2 weeks plus ipilimumab at 1 mg/kg (IPI1) every 6 weeks; or nivolumab at 1 mg/kg (NIVO1) every 3 weeks plus ipilimumab at 3 mg/kg (IPI3) every 3 weeks for 4 cycles followed by nivolumab at 240 mg every 2 weeks.

The objective response rate (ORR) was 26% (95% CI, 9%-51%) in the monotherapy arm, 31% (95% CI, 18%-47%) with NIVO3 plus IPI1, and 40% (95% CI, 26%-56%) with NIVO1 plus IPI3. The median duration of response was not reached in the monotherapy group and was between 24.4 months and 34.1 months in the combination groups.

“Our results suggest that nivolumab plus ipilimumab or other dual immunotherapy regimens should be further investigated as a potential backbone of immunotherapy for patients with recurrent or metastatic cervical cancer. Long-term data for the nivolumab monotherapy group show that this agent continues to be a viable treatment option in the second-line or later-line setting for patients with recurrent or metastatic cervical cancer,” the study authors wrote.

A total of 19 patients were enrolled in the monotherapy arm, 45 in the NIVO3 plus IPI1 arm, and 45 in the NIVO1 plus IPI3 arm. Baseline characteristics included a median age of 51.0, 48.0, and 44.0 years; 95%, 56%, and 60% of patients were from Europe; and 89%, 76%, and 76% of patients were White across all 3 treatment groups. Additionally, across all groups, most patients had an ECOG performance status of 0 (53%, 51%, and 56%); 61%, 62%, and 66% had a PD-L1 expression of 1% or more; and 63%, 56%, and 53% had metastatic disease in their lymph nodes.

The database lock was December 13, 2021, and the median follow-up times were 19.9 months in the monotherapy arm, 12.6 months in the NIVO3 plus IPI1 arm, and 16.7 months in the pooled NIVO1 plus IPI3 group. The minimum follow-up times for overall survival (OS) in each respective group were 67.4 months, 36.9 months, and 17.9 months. Two patients remained on treatment in the NIVO1 plus IPI3 group after the database lock.

In the nivolumab monotherapy group, the median progression-free survival was 5.1 months, (95% CI, 1.9-9.1), 3.8 months (95% CI, 2.1-10.3) in the NIVO3 plus IPI1 group, and 7.2 months (95% CI, 3.8-17.2) in the NIVO1 plus IPI3 group. In each arm, the median OS was 21.6 months (95% CI, 8.3-46.9), 15.2 months (95% CI, 9.0-36.2), and 24.7 months (95% CI, 16.6-49.1), respectively.

Complete response rates observed in the monotherapy, NIVO3 plus IPI1, and NIVO1 plus IPI3 groups included 21%, 7%, and 11%; partial response rates were 5%, 24%, and 29%; stable disease was reported in 42%, 31%, and 31%; and progressive disease was highlighted in 31%, 36%, and 24%.

A total of 63% of patients in the monotherapy group, 80% in the NIVO3 plus IPI1 arm, and 88% in the pooled NIVO1 plus IPI3 group experienced treatment-related adverse effects (TRAEs). Grade 3/4 TRAEs occurred in 21%, 29%, and 46%, respectively. Additionally, 11%, 18%, and 24% of patients from each group discontinued treatment due to any-grade TRAEs. The most common grade 3 TRAEs included diarrhea (5% vs 2% vs 2%) and pneumonitis (5% vs 0% vs 4%) across all arms, respectively.

Grade 3/4 immune-mediated AEs leading to discontinuation were pneumonitis (5%) in the monotherapy group; hepatitis (4%) and nephritis or renal dysfunction (2%) in the NIVO3 plus IPI1 group; and hepatitis (8%), diarrhea or colitis (3%), pneumonitis (3%), and rash (1%) in the pooled NIVO1 plus IPI3 group. In the NIVO1 plus IPI3 group, 1 patient died from immune-mediated colitis related to treatment.

Reference

Oaknin A, Moore K, Meyer T, et al. Nivolumab with or without ipilimumab in patients with recurrent or metastatic cervical cancer (CheckMate 358): a phase 1-2, open-label, multicohort trial. Lancet Oncol. 2024;25(5):588-602. doi:10.1016/S1470-2045(24)00088-3