Neoadjuvant nivolumab plus ipilimumab followed by chemoradiation (RT-CT) and maintenance nivolumab yields high survival rates in locally advanced cervical cancer (LACC), according to final survival data from the phase II COLIBRI-1 trial.
Over a median follow-up of 40 months, the 3-year overall survival (OS) rate was 90 percent (95 percent confidence interval [CI], 76–96), and the 3-year progression-free survival (PFS) rate was 83 percent (95 percent CI, 67–91), reported lead investigator Dr Florence Joly from Centre François Baclesse in Caen, France. [ESMO GYN 2026, abstract 27O]
When stratified according to FIGO 2018 stage, the respective 3-year OS and PFS rates were 100 percent and 93 percent among patients with stage I-II disease and 85 percent and 77 percent among those with stage III-IV disease.
Immune microenvironment
Joly and colleagues evaluated the immune microenvironment using 69 paired biopsies collected at baseline and after completion of neoadjuvant combination immunotherapy/before RT-CT (post-induction).
Thirty-two paired biopsies were analysed using 7-colour multiplex immunofluorescence tissue imaging (multi-IF) to quantify total and proliferating CD8+ and total FOXP3+ cell densities. A median CD8+/FOXP3+ ratio of 4.43 was the threshold for patient stratification. Then, 37 paired biopsies underwent transcriptomic analysis using high-throughput genomic sequencing (HTG), which enabled classification of tumours as immunologically active (‘hot’) or inactive (‘cold’).
Multi-IF data showed that patients with a CD8+/FOXP3+ ratio at or below the median both at baseline and post-induction had less favourable survival outcomes, Joly noted.
The 3-year OS and PFS rates were 95 percent and of 89 percent, respectively, among patients with a baseline CD8+/FOXP3+ ratio above the median vs 85 percent and 75 percent, respectively, among those with a baseline CD8+/FOXP3+ ratio at or below the median.
The difference in survival rates was even more pronounced when looking at post-induction CD8+/FOXP3+ ratios. The respective 3-year OS and PFS rates were 94 percent and 94 percent among patients with a ratio above the median vs 81 percent and 63 percent among those with a ratio at or below the median.
Looking at immune signature based on the HTG data, Joly pointed out that patients whose tumours remained completely unresponsive and persistently had a ‘cold’ score at baseline and post-ICB had poorer survival outcomes than those who had a ‘hot’ score at either baseline or post-induction or those who converted from ‘cold’ to ‘hot’ post-induction. This trend held for both PFS and OS.
Safety profile
No new safety signals emerged during the follow-up, according to Joly.
Grade ≥2 adverse events (AEs) occurred in 35 percent of patients during neoadjuvant treatment, 85 percent during RT-CT, and 41 percent during maintenance therapy. Grade 3/4 treatment-related AEs were reported in 2.5 percent, 30 percent, and 20 percent of patients, respectively. There were no AEs that resulted in death.
COLIBRI-1 trial
COLIBRI-1 was a multicentre, single-arm pilot study involving 40 women (median age 55 years) with histologically confirmed cervical adenosquamous carcinoma, FIGO 2018 stage IB3 to IVA disease, and ECOG performance status of 0 or 1.
The treatment schedule consisted of a neoadjuvant treatment phase in which patients received a single cycle of intravenous ipilimumab 1 mg/kg on day 1 plus nivolumab 3 mg/kg on days 1 and 15. This was followed by 5 to 8 weeks of RT-CT and a 4-to-6-week delay. After RT-CT, patients received nivolumab 480 mg every 4 weeks for 6 months as maintenance. If required, patients underwent surgery for residual disease.
At baseline, FIGO 2018 disease stage was IB3 in 3 percent of patients, IIA2 in 3 percent, IIB in 30 percent, IIIB in 3 percent, IIIC1 in 25 percent, IIIC2 in 25 percent, and IVA in 13 percent. More than 90 percent of patients had squamous cell carcinoma (95 percent) and had PD-L1 expression of ≥1 (93 percent).
All 40 patients received the full neoadjuvant immunotherapy combination treatment and received EBRT per protocol. Chemotherapy during radiotherapy was cisplatin in 97.5 percent of patients and carboplatin in 7.5 percent. Brachytherapy was delivered in 36 patients. Of the 39 patients who entered the maintenance phase, 34 completed all 6 cycles of nivolumab maintenance.