March 25 2023
Locally advanced cervical cancer remains an area of high therapeutic need, with recent trials failing to demonstrate evidence of benefit from adjuvant chemotherapy or immune checkpoint blockade administered concurrent with chemoradiation. Results from the NRG-GY017 randomized trial comparing the anti-PD-L1 inhibitor atezolizumab before and concurrent with chemoradiation (CRT) indicated favorable outcomes for 2-year disease-free survival (DFS) and demonstrated evidence of improved immunogenicity with neoadjuvant atezolizumab in patients with locally advanced cervical cancer. These findings were presented during the Plenary Session at the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer and the abstract was the recipient of the SGO 2023 Presidential Award.
NRG-GY017 accrued 36 patients with pelvic or para-aortic lymph-node-positive, locally advanced cervical cancer and randomly assigned patients to receive either atezolizumab prior to and concurrently with CRT on treatment arm A or only atezolizumab concurrently with CRT on treatment arm B. Patients on Arm A received atezolizumab on days -21, 0, and 21 with CRT whereas patients on Arm B received atezolizumab on days 21 and 42 with CRT.
Median follow-up for this study was 25.8 months. The proportion of patients on Arm A with 2-year DFS was 79% versus 59% in Arm B (p=0.28). Patients in Arm A had a 69% pathologically complete or partial response compared to 40% in Arm B of the 31 patients with day 28 post-treatment biopsy data available.
There was no association found between the baseline PD-L1 status and 2-year DFS. Twenty-two patients had available baseline tumor and 80% in Arm A versus 75% in Arm B had positive PD-L1 immune infiltrate scoring (p=0.59). Arm A had 30% positive tumor cell PD-L1 scoring versus 83% in Arm B (p=0.02). Both were defined as straining at 1% or above.
“In addition to the favorable results discovered in this data, it is also crucial to note that there was an early decrease in T-cell receptor diversity and potential killing of tumor-associated T-cell receptor clones with concurrent chemoradiation, which could imply harmful consequences for immune response. This information warrants further clinical studies navigating differential sequencing of chemoradiation and immune checkpoint blockade,” stated Dmitriy Zamarin, MD PhD of Memorial Sloan Kettering Cancer Center and the lead author of the NRG-GY017 abstract.
In this analysis, patients had T-cell receptor (TCR) repertoire sequencing data from all timepoints. Therapy led to TCR clonal expansion in both arms, though the majority of the TCR clones were not found in tumors. The fraction of tumor-associated TCR clones that expanded in peripheral blood in response to therapy was larger in Arm A. While atezolizumab led to initial peripheral expansion of tumor-associated TCR clones in Arm A, some of the clones contracted in response to the subsequent CRT following the first cycle of treatment.
This project was supported by grants U10CA180868 (NRG Oncology Operations) and U10CA180822 (NRG Oncology SDMC) from the National Cancer Institute (NCI).
Citation
Zamarin D, Deng W, Lankes HA, Ghamande S, Holman L, Mathews CA, Park K, Banberry B, Sherry N, Kim H, Sharon E, Aghajanian C, O'Cearbhaill R, Schilder R, Mayadev J. Evolution of peripheral and tumor immune parameters as biomarkers of differential sequencing of immune checkpoint blockade and chemoradiotherapy in locally advanced cervical cancer: An NRG Oncology/GOG Study. SGO (Society of Gynecologic Oncology).
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to conduct clinical trials with emphasis on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.
www.nrgoncology.org