After comparing the efficacy of the anti–PD-L1 inhibitor atezolizumab prior to and concurrently with chemoradiation, researchers have indicated favorable outcomes for 2-year disease-free survival and demonstrated evidence of improved immunogenicity with neoadjuvant atezolizumab in patients with locally advanced cervical cancer, according to findings presented by Zamarin et al during the Plenary Session of the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer.
Locally advanced cervical cancer remains an area of high therapeutic need, with recent trials failing to demonstrate the benefits of adjuvant chemotherapy or immune checkpoint inhibitors administered concurrently with chemoradiation.
Study Methods and Results
In the novel NRG-GY017 randomized trial (ClinicalTrials.gov identifier NCT03738228), researchers randomly assigned 36 patients with pelvic or para-aortic lymph node–positive, locally advanced cervical cancer to receive either atezolizumab prior to and concurrently with chemoradiation (treatment arm A) or atezolizumab only concurrently with chemoradiation (treatment arm B). The patients in arm A received atezolizumab 21 days before and on day 0 and 21 of chemoradiation, whereas patients in arm B received atezolizumab on days 21 and 42 of chemoradiation.
After a median follow-up of 25.8 months, the researchers discovered that 79% of the patients in arm A vs 59% of the patients in arm B (P = .28) experienced a 2-year disease-free survival. Additionally, among the 31 patients with posttreatment biopsy data collected after 28 days, those in arm A had a 69% pathologically complete or partial response to treatment compared with 40% of those in arm B.
The researchers noted that there was no association found between the patients’ baseline PD-L1 status and 2-year disease-free survival. Twenty-two patients had available baseline tumors, and 80% in arm A vs 75% in arm B (P = .59) had PD-L1–positive immune infiltration scores (ie, ≥ 1% of tumor volume). Further, the patients in arm A had a 30% rate of PD-L1–positive tumor cell scores compared with 83% of those in arm B (P = .02).
Conclusions
In their analysis, the researchers revealed that patients had T-cell receptor repertoire sequencing data from all time points. Therapy led to T-cell receptor clonal expansion in both arms of the study, though the majority of the clones were not found in the tumors. The fraction of tumor-associated clones that expanded into peripheral blood in response to the therapy was larger for patients in arm A. Although atezolizumab led to initial peripheral expansions of tumor-associated clones for patients in arm A, some of the clones contracted in response to the subsequent chemoradiation following the first cycle of treatment.
“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 [inhibitors],” said lead study author Dmitriy Zamarin, MD PhD, Director of Translational Research at Memorial Sloan Kettering Cancer Center.
Disclosure: This research was supported by grants from the National Cancer Institute.
