Pre- and Co-administration of Nivolumab Proves Safe in Locally Advanced Cervical Cancer Treated With CCRT

The addition of the pre- and co-administration of nivolumab (Opdivo) with concurrent chemoradiation (CCRT) appeared to be safe and feasible in patients with locally advanced cervical carcinoma, according to data from the phase 1 GOTIC-018 trial (JMA-IIA00425).¹

Among those in cohort A, those who received nivolumab with CCRT and nivolumab maintenance, the complete response (CR) rate was 73.3% (n = 11), and the partial response (PR) rate was 26.7% (n = 4). Among those in cohort B, those who received induction treatment with nivolumab plus nivolumab with CCRT and nivolumab maintenance, the PR rate was 6.7% (n = 1), and the stable disease rate was 93.3% (n = 14).

“No dose-limiting toxicity [DLT] was reported during the acute phase in both cohort A and B, and no new safety signals were observed,” lead study author Akira Yabuno, of the Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan, and colleagues, wrote in a poster on the data. “Further studies assessing the safety and efficacy of pre-administration of nivolumab in patients with locally advanced cervical cancer with CCRT are needed.”

CCRT represents the current standard of care for patients with locally advanced cervical carcinoma. In those with non–small cell lung cancer, CCRT followed by immune checkpoint inhibition has significantly impacted clinical practice. In those with recurrent or metastatic cervical cancer, nivolumab has demonstrated a promising signal of activity; however, the safety and feasibility of nivolumab plus CCRT has yet to be reported in this population.

With the multicenter, prospective, open-label GOTIC-018, investigators sought to examine the safety and feasibility of pre- and co-administration of nivolumab with CCRT in those with locally advanced cervical carcinoma. The trial enrolled those with FIGO 2008 stage IB2 to IVA disease.

In cohort A, 15 patients received nivolumab at 240 mg every 2 weeks in combination with, and following, CCRT. CCRT was comprised of EBRT followed by vaginal brachytherapy with cisplatin at 40 mg/m2 once weekly for 4 or more cycles. In cohort B, 15 patients received nivolumab before, in combination with, and following CCRT. For the latter cohort, 2 cycles of nivolumab were given prior to the start of CCRT. The sample size for the trial was 30 patients.

The first 6 patients were enrolled for evaluation of DLTs in each cohort; if 0 or 1 patient experienced DLTs, an additional 9 patients were enrolled to each cohort. For cohort A, the DLT evaluation period ranged from nivolumab was administered to 28 days after the end of CCRT. For cohort B, this DLT evaluation period ranged from the start of CCRT to 28 days following CCRT completion.

Patients were enrolled to the trial from March 2019 to September 2020. The median age of patients in cohort A was 50 years (range, 26-73) vs 56 years (range, 41-71) in cohort B. Most patients in cohorts A and B had an ECOG performance status of 0 (93.3% vs 100%) and squamous cell carcinoma histology (93.3% vs 93.3%). Patients in cohorts A and B had FIGO stage IB2 (6.7% vs 6.7%, respectively), IIA (6.7% vs 0%), IIB (60.0% vs 40.0%), IIIB (26.7% vs 46.7%), or IVA (0% vs 6.7%) disease. In cohort A, 20% of patients had lymph node metastasis vs 60% of those in cohort B.

In the first 6 patients evaluable for DLTs in each cohort, no DLTs were observed. As such, the study was expanded to enroll an additional 9 patients in each cohort.

Any-grade adverse effects (AEs) were experienced by all patients. The most common grade 3 or higher AEs experienced by cohorts A and B, respectively, were anemia (13.3% vs 26.7%), leukopenia (86.7% vs 66.7%), neutropenia (60.0% vs 26.7%), thrombocytopenia (20.0% vs 0%), increased amylase (6.7% vs 0%), increased lipase (6.7% vs 6.7%), increased alanine aminotransferase (6.7% vs 6.7%), decreased appetite (13.3% vs 0%), colitis (0% vs 6.7%), and diarrhea (13.3% vs 20.0%).

No serious immune-relate toxicities were experienced in either cohort nor did any deaths occur. No patients needed to delay starting CCRT because of AEs associated with the pre-administration of nivolumab in cohort B.

In cohort A, the median number of cycles of cisplatin received was 5 (range, 3-6). Forty percent of patients required cisplatin interruption, 13.3% required dose reduction of cisplatin, and 6.7% required discontinuation of the agent. EBRT interruption was required in 13.3% of patients. The number of cycles of nivolumab was 6 (range, 1-7); this agent was interrupted in 53.3% of patients and discontinued in 6.7% of patients.

In cohort B, the median number of cisplatin cycles received was 6 (range, 4-6); this agent was interrupted in 40.0% of patients and discontinued in 6.7% of patients. The number of cycles of nivolumab received was 9 (range, 3-9); this agent was interrupted in 40.0% of patients and discontinued in 6.7% of patients.

Reference

1. Yabuno A, Nakamura K, Satoh T, et al. GOTIC-018: phase I open-label, multicenter study to assess the safety of pre- and co-administration of ONO-4538 (nivolumab) with concurrent chemoradiation (CCRT) in patients (pts) with locally advanced cervical carcinoma (LACvCa). J Clin Oncol. 2022;40(suppl 16):5529. doi:10.1200/JCO.2022.40.16_suppl.5529