Document Type
Article
Publication Date
1-9-2025
Abstract
Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC. The primary endpoint was the fraction of expanded tumor-associated T-cell receptor (TCR) clones in blood at day 21 as a surrogate measure of anti-tumor immune response. Secondary objectives were safety and feasibility, 2-year disease-free survival (DFS), and predictive value of PD-L1 expression. Forty patients were randomized, 36 received treatment, and 25 were evaluable for the primary endpoint. After cycle 1, there was peripheral expansion of higher proportion of tumor-associated TCR clones in Arm A than in Arm B (p = 0.0025) that remained higher at day 21, meeting the pre-specified endpoint on two-sample T-test (p = 0.052), but not on sensitivity analysis by Wilcoxon test (p = 0.13). At the median follow up of 25.8 months, 2-year DFS was 76% in Arm A and 56% in Arm B (p = 0.28). There were no new safety signals. In conclusion, neoadjuvant ICB prior to CRT was safe and was associated with immunologically and clinically favorable outcomes, warranting larger confirmatory studies.
Recommended Citation
Mayadev, Jyoti; Zamarin, Dmitriy; Deng, Wei; Lankes, Heather A.; Pesci, Giulio; Kim, Hayeon; Chino, Junzo P.; Banbury, Barbara; Sherry, Ned; Sharon, Elad; Ghamande, Sharad A.; Ferguson, Catherine; Mell, Loren; Holman, Laura; Mathews, Cara; O'Malley, David; Olawaiye, Alexander; Hopp, Elizabeth; Leath, Charles; Copeland, Larry; Mannel, Robert; O'Cearbhaill, Roisin; Aghajanian, Carol; and Schilder, Russell J., "Neoadjuvant or Concurrent Atezolizumab with Chemoradiation for Locally Advanced Cervical Cancer: a Randomized Phase I Trial" (2025). Department of Medical Oncology Faculty Papers. Paper 283.
https://jdc.jefferson.edu/medoncfp/283
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Supplementary Materials 1
41467_2024_55200_MOESM2_ESM.pdf (459 kB)
Supplementary Materials 2
41467_2024_55200_MOESM3_ESM.pdf (1048 kB)
PubMed ID
39788967
Language
English
Comments
This article is the author's final published version in Nature Communications, Volume 16, Issue 1, January 2025, page 553.
The published version is available at https://doi.org/10.1038/s41467-024-55200-2.
Copyright © The Author(s) 2025.