Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: A randomized phase I trial Journal Article
| Authors: | Mayadev, J.; Zamarin, D.; Deng, W.; Lankes, H. A.; Pesci, G.; Kim, H.; Chino, J. P.; Banbury, B.; Sherry, N.; Sharon, E.; Ghamande, S. A.; Ferguson, C.; Mell, L.; Holman, L.; Mathews, C.; O'Malley, D.; Olawaiye, A.; Hopp, E.; Leath, C. 3rd; Copeland, L.; Mannel, R.; O'Cearbhaill, R.; Aghajanian, C.; Schilder, R. J. |
| Article Title: | Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: A randomized phase I trial |
| 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. © 2025. The Author(s). |
| Keywords: | adult; controlled study; aged; disease-free survival; middle aged; genetics; clinical trial; mortality; disease free survival; neoadjuvant therapy; metabolism; randomized controlled trial; pathology; monoclonal antibody; immunology; receptors, antigen, t-cell; phase 1 clinical trial; drug therapy; uterine cervical neoplasms; therapy; uterine cervix tumor; lymphocyte antigen receptor; chemoradiotherapy; programmed death 1 ligand 1; procedures; immune checkpoint inhibitor; antibodies, monoclonal, humanized; humans; human; female; immune checkpoint inhibitors; atezolizumab; cd274 protein, human; b7-h1 antigen |
| Journal Title: | Nature Communications |
| Volume: | 16 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2025-01-09 |
| Start Page: | 553 |
| Language: | English |
| DOI: | 10.1038/s41467-024-55200-2 |
| PUBMED: | 39788967 |
| PROVIDER: | scopus |
| PMCID: | PMC11718273 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed (through Conflict of Interest Statement) and PDF -- Source: Scopus |
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