Nivolumab ± Ipilimumab Yields Meaningful, Durable Responses in Recurrent or Metastatic Cervical Cancer


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

Related Videos
Brian Slomovitz, MD, MS, FACOG discusses the use of new antibody drug conjugates for treating patients with various gynecologic cancers.
Developing novel regimens may continue to improve survival outcomes of patients with advanced cervical cancer following the FDA approval of pembrolizumab and chemoradiation, says Jyoti S. Mayadev, MD.
Treatment with pembrolizumab plus chemoradiation appears to be well tolerated with no detriment to quality of life among those with advanced cervical cancer.
Jyoti S. Mayadev, MD, says that pembrolizumab in combination with chemoradiation will be seamlessly incorporated into her institution’s treatment of those with FIGO 2014 stage III to IVA cervical cancer following the regimen’s FDA approval.
Despite the addition of a TIGIT inhibitor to a checkpoint inhibitor resulting in high levels of safety, there is no future for that combination alone, according to Ritu Salani, MD.
Treatment with tisotumab vedotin may be a standard of care in second- or third-line recurrent or metastatic cervical cancer, says Brian Slomovitz, MD, MS, FACOG.
Domenica Lorusso, MD, PhD, says that paying attention to the quality of chemoradiotherapy is imperative to feeling confident about the potential addition of pembrolizumab for locally advanced cervical cancer.
Guidelines from the Society of Gynecologic Oncology may help with managing the ongoing chemotherapy shortage in the treatment of patients with gynecologic cancers, according to Brian Slomovitz, MD, MS, FACOG.
Related Content