The 24-month follow-up of the phase 1/2 CheckMate 358 trial found nivolumab with or without ipilimumab yielded clinically meaningful, long-lasting responses in patients with recurrent or metastatic cervical cancer.
Nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) yielded a sustained, clinically meaningful response in patients with recurrent or metastatic cervical cancer, according to the 24-month follow-up findings of the phase 1/2 CheckMate 358 trial (NCT02488759).
The objective response rate (ORR) in patients receiving nivolumab monotherapy (n = 19) was 26% (95% CI, 9%-51%). Moreover, the ORR was 31% (95% CI, 18%-47%) when nivolumab was given at a dose of 3 mg and ipilimumab at 1 mg in the overall population (n = 45). Additionally, in the expansion cohort (n = 112), a regimen consisting of nivolumab at 1 mg plus ipilimumab at 3 mg, the ORR was 38% (95% CI, 29%-48%) in the overall population. For patients who received nivolumab at 3 mg plus ipilimumab at 1 mg in the frontline, the ORR was 39% (95% CI, 17%-64%) and 26% (95% CI, 11%-46%) in the second-line or later setting. For those in the expansion cohort, the ORR was 41% (95% CI, 29%-53%) in the first line and 35% (95% CI, 21%-51%) in the second line or later.
Treatment continued for a maximum of 24 months, until disease progression, unacceptable toxicity, or withdrawal of consent. Imaging was conducted every 8 weeks for 1 year, then every 12 weeks thereafter. Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
Patient had a median age of 51 years in the monotherapy arm, 48 years in the combination arm, and 46 years in the expansion arm. In total, 21%, 40%, and 64% of patients in each respective arm had an ECOG performance status of 0. Of note, 21% of patients in the monotherapy group, 40% in the combination group, and 64% in the expanded cohort received no prior systemic therapies in the metastatic setting. Additionally, 42%, 44%, and 28% of patients, respectively, received 1 prior line of therapy, and 37%, 16%, and 8% had 2 prior lines of therapy.
The median DOR was not reached (NR; 95% CI, 35.3-NR) in the monotherapy arm. Moreover, median DOR was 24.4 months (95% CI, 8.7-NR) in the overall combination arm, 34.6 months (95% CI, 6.6-NR) in the first-line combination treatment arm, and 21.1 months (95% CI, 7.5-NR) in second-line or later combination arm. For patients in the expanded cohort, the median DOR was 34.1 months (95% CI, 11.5-NR) in the overall population, 25.6 months (95% CI, 9.2-NR) in the first-line setting, and NR (95% CI, 5.2-NR) in the second-line setting.
The median OS was 21.6 months (95% CI, 8.3-46.9) in the single-agent nivolumab arm; moreover, the 12-month OS rate in the cohort was 73% (95% CI, 46%-88%) and 43% (95% CI, 20%-64%) at 24 months. In the combination group, the median OS was 15.2 months (95% CI, 9.0-36.2), and the 12-month and 24-month OS rates were 54% (95% CI, 38%-68%), and 37% (95% CI, 23%-51%), respectively. In the expanded cohort, the median OS was 20.9 months (95% CI, 14.4-32.8). The 12-month OS rate in this group was 69% (95% CI, 60%-77%), and at 24 months it was 48% (95% CI, 38%-57%).
The investigator assessed median PFS was 5.1 months (95% CI, 1.9-9.1) in the monotherapy group, 3.8 months (95% CI, 2.1-10.3) in the combination group, and 5.8 months (95% CI, 3.8-9.3) in the expansion cohort.
Grade 3/4 treatment-related adverse effects (TRAEs) in the monotherapy group occurred in 21% of patients, 29% in the combination group, and 46% in the expanded cohort. Moreover, grade 3/4 TRAEs leading to discontinuation occurred in 5%, 9%, and 19% of patients, respectively. The most common serious grade 3/4 TRAEs in the combination and expansion cohorts, respectively, were hepatitis (7% vs 16%) and diarrhea/colitis in (2% vs 5%). There was only 1 treatment-related death that occurred in the expansion cohort.
Oaknin A, Moore KN, Meyer T, et al. Safety and efficacy of nivolumab (NIVO) ± ipilimumab (IPI) in patients (pts) with recurrent/metastatic cervical cancer (R/M Cx Ca) in checkmate 358. Annal Oncol. 2022;33(suppl 7):520M0. doi:10.1016/annonc/annonc1054