Is there a role for intensification immunotherapy in patients with locally advanced cervical cancer?

Final survival data and immune subgroup exploratory analyses from the COLIBRI-1 trial, as presented at ESMO Gynaecological Cancers 2026 (Copenhagen, 17–19 June), suggest that induction immunotherapy may help induce a strong immune response in locally advanced cervical cancer (LACC), providing proof of concept that this approach is feasible and does not negatively impact subsequent chemoradiotherapy (CRT) (Abstract 27O)

The benefits of adding immunotherapy to CRT in patients with LACC were previously demonstrated in the phase III KEYNOTE-A18 trial where significantly improved survival outcomes were reported with the addition of pembrolizumab to CRT, leading to approval for patients with higher-risk, stage III–IVA disease (Lancet. 2024;403:1341–1350; Lancet. 2024;404:1321–1332).

Induction immunotherapy is believed to act synergistically with CRT through an abscopal effect to provide systemic disease control. Previous data from the phase II COLIBRI-1 study suggested that induction immunotherapy for LACC was able to prime tumours, leading to an improved response to standard CRT (Nat Commun. 2026;17:922).

In the study, 40 patients with FIGO 2018 stage IBIII–IVA LACC received induction nivolumab plus ipilimumab, followed by standard chemoradiotherapy (CRT) and 6 months of maintenance nivolumab. Exploratory subgroup analyses were performed according to baseline immune features, including transcriptomic ‘hot’ status and CD8⁺/FOXP3⁺ ratio.

At a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 83% and 90%, respectively. In patients with FIGO stage I–II LACC, no deaths had occurred at 3 years (100% OS rate), and PFS was 93%. In those with FIGO stage III–IV disease, 3-year OS and PFS rates were 85% and 77%, respectively. Patients developing an immune reaction (‘hot’ score) following induction immunotherapy experienced better survival than those with persistent ‘cold-cold’ tumours.

“The immune subgroup analyses clearly show improved responses in patients with immune activated tumours, and the high OS and PFS rates at 40 months’ follow-up suggest that many patients are cured of their disease,” notes Dr Domenica Lorusso from Humanitas Hospital San Pio X, Milan, Italy, commenting on the data.

No new safety signals were observed in the 40 participants. Grade 3–4 adverse events possibly related to treatment were reported in 1 patient (2.5%) during neoadjuvant therapy, 12 patients (30.0%) with CRT and 8 patients (20.0%) during maintenance nivolumab therapy. “The current data suggest that the benefits of immunotherapy in the longer term are not offset by significant toxicity in this small study,” she remarks.

Also reported at the Congress were encouraging findings for adjuvant immunotherapy in LACC from an interim analysis of a second phase II trial (ATOMICC), in which patients were randomised to observation or dostarlimab for up to 2 years (Abstract 26O). Maintenance dostarlimab was associated with a 3-year PFS rate of 77% (versus 67% with observation) after CRT in 134 patients with high-risk disease at a median follow-up of 40.6 months. PFS events had occurred in 34 of 74 patients (46%) required for final analysis; the PFS benefit numerically favoured the dostarlimab arm but did not reach statistical significance (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.31–1.31).

Lorusso notes that, “While the PFS difference is not significant, there is a signal at interim analysis suggesting activity of adjuvant immunotherapy in this setting and it will be interesting to see updated data with additional monitoring.”

Grade ≥3 adverse events were reported in 36% of patients receiving dostarlimab (most commonly diarrhoea and asthenia) and 24% of those on observation; 1 patient in the dostarlimab arm died from duodenal perforation that was considered unrelated to treatment.
While current evidence indicates that there may not be a role for intensification immunotherapy for all patients with LACC, some may not require long-term maintenance immunotherapy. “Data from the COLIBRI-1 study show that patients with stage I–II disease achieve 100% OS at 12 months that is maintained at 3 years, suggesting that 2 years’ maintenance may not be needed in these good-prognosis patients, and CRT alone may even be sufficient,” Lorusso adds.

Additional investigations are needed to explore optimal immunotherapy plus CRT combinations in LACC. Further insights will be provided by COLIBRI-2, an ongoing phase II trial comparing induction and maintenance nivolumab plus relatlimab (anti-LAG-3) with nivolumab in patients with FIGO stage IIB–IVA LACC (NCT06715241).