Patients
Forty patients were enrolled, with 36 eligible and treated (19 in Arm A and 17 in Arm B). The median age was 48 years, with a diverse ethnic background. Pre-treatment PET/CT scans indicated various lymph node involvements.
Safety
Treatment-related grade 3 or higher adverse events were documented, with Arm A showing no dose-limiting toxicities (DLTs) and Arm B reporting three DLTs. Most patients completed their treatment, with a high percentage receiving the intended doses of atezolizumab and cisplatin, and completing external beam radiation therapy (EBRT) and brachytherapy.
Efficacy
The study recorded a 2-year disease-free survival (DFS) rate of 76% in Arm A and 56% in Arm B, with no significant difference between the arms. The presence of para-aortic lymph nodes (PALN) was associated with shorter DFS and overall survival (OS).
Evolution of TCR Repertoire in Response to Therapy
Significant changes in T-cell receptor (TCR) diversity and clonal expansion were observed in response to treatment, with a notable decrease in TCR diversity during the chemoradiation therapy (CRT) phase. The study also explored the association between TCR repertoire evolution and clinical outcomes, finding a negative correlation between TCR clone expansion and 2-year DFS.
Conclusion
The NRG-GY017 trial provides valuable insights into the sequencing of immunotherapy and CRT in locally advanced cervical cancer, highlighting the potential benefits of neoadjuvant atezolizumab. The study's findings on TCR repertoire evolution and its association with clinical outcomes offer a foundation for future research in optimizing treatment strategies for cervical cancer.
