212 - Long-Term Outcomes of Definitive Chemoradiotherapy Plus Toripalimab for Locally Advanced Cervical Cancer: A Single-Center Phase II Trial with Integrated Pretreatment Transcriptomic Correlatives
Presenter(s)
Y. J. Cao1, C. Li1, S. Zhang2, X. Sun2, J. J. Chen1, and Z. Yuan3; 1Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer and Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China, 2Department of Radiation Oncology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China, 3Department of Radiation Oncology, CyberKnife Center, and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
Purpose/Objective(s): We hypothesized that definitive CCRT plus toripalimab yields favorable long-term disease control with acceptable grade =3 toxicity in treatment-naïve locally advanced cervical cancer (LACC), and that pretreatment immune–stromal transcriptomic states are associated with early complete response (CR) and long-term survival.
Materials/Methods: Single-center, open-label, phase II trial enrolled 82 patients with treatment-naïve LACC; median follow-up 41.2 months. Treatment: standard definitive CCRT with brachytherapy plus toripalimab. Endpoints: 6-month MRI response (RECIST v1.1), long-term overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), and grade =3 treatment-related toxicities (CTCAE). Pretreatment bulk RNA-seq was available for 71 patients; differential expression used DESeq2 (|log2FC|=1, FDR<0.05) with immune/stromal inference (ESTIMATE/CIBERSORT). An exploratory 3-gene score (BCAT1/CXCL2/ITGA5) was evaluated for prognostic discrimination in TCGA-CESC with external validation in CGCI-HTMCP-CC using time-dependent AUC.
Results: In the clinical trial cohort, 3-year outcomes were: OS 77.9%, PFS 76.8%, LRFS 94.3%, RRFS 98.0%, and DMFS 86.2%. Grade =3 toxicities included anemia 13.9%, neutropenia 9.7%, lymphopenia 79.1%, thrombocytopenia 4.1%, acute urinary 1.3%, acute gastrointestinal 0%, late urinary 1.7%, and late gastrointestinal 2.5%; any immune-related toxicity occurred in 29.1%. Among 71 evaluable patients with transcriptomics, 47 (66%) achieved CR and 24 (34%) were non-CR at 6 months. Pretreatment transcriptomics showed CR enrichment of B-cell/immunoglobulin programs, whereas non-CR was characterized by chemotaxis/inflammatory myeloid–neutrophil signatures with higher immune/stromal scores and lower estimated tumor purity. In TCGA-CESC, the 3-gene score showed moderate discrimination for OS (AUC 0.708/0.728/0.694 at 1/3/5 years) with consistent separation in an external cohort.
Conclusion: Definitive CCRT plus toripalimab demonstrated encouraging long-term disease control with low rates of severe non-hematologic toxicity in a single-center phase II LACC cohort. Pretreatment immune–stromal transcriptomic states were associated with early CR and support biomarker-driven risk stratification; prospective multicenter validation is warranted.
Abstract 212 – Table 1| Category | Endpoint | Value |
|---|---|---|
| Follow-up | Median follow-up (months) | 41.2 |
| Response | 6-month CR / non-CR | 66% / 34% |
| Efficacy | 3-year OS / PFS | 77.9% / 76.8% |
| Efficacy | 3-year LRFS / RRFS / DMFS | 94.3% / 98.0% / 86.2% |
| Safety | Any immune-related toxicity | 29.1% |
| Safety (=G3) | Anemia / Neutropenia / Lymphopenia / Thrombocytopenia | 13.9% / 9.7% / 79.1% / 4.1% |
| Safety (=G3) | Acute urinary / acute GI | 1.3% / 0% |
| Safety (=G3) | Late urinary / late GI | 1.7% / 2.5% |