Jyoti S. Mayadev, MD, on Atezolizumab for Locally Advanced, Node-Positive Cervical Cancer

CancerNetwork® sat down with Jyoti S. Mayadev, MD, associate professor of Radiation Medicine and Applied Sciences and assistant vice chair in Developmental Therapeutics and Section Chief of Gynecologic Oncology at UC San Diego School of Medicine, at The Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer to discuss the phase 1 NRG-GY017 trial (NCT03738228) trial that showed promised of atezolizumab (Tecentriq) in the setting of locally advanced cervical cancer.

Atezolizumab, a PD-L1 inhibitor used either before as an immune primer and/or with chemoradiotherapy, led to promising outcomes in terms of progression-free survival and safety for patients with node-positive disease in stages IB2, II, IIIB, or IVA.

Transcript:

We chose a population with high-risk, node-positive [disease], including periodic node-positive cervical cancer because these patients represent an unmet need. They have recurrence rates of up to 60% after standard chemoradiation, and we know that cervical cancer is an immunogenic disease. Therefore, we try to use immune primers to stimulate the immune system using anti–PD-L1 immune checkpoint blockade before and during chemoradiation. We also tried to look at the difference in immunogenicity between the 2 arms of the trial—the priming arm vs the concurrent [therapy] arm—to determine if that would be a signal for response and overall survival.

The key highlights are that it is safe to combine an immune checkpoint blockade like atezolizumab, or an anti–PD-L1 agent, with chemoradiation and we observed very low DLTs [dose-limiting toxicities] in patients who responded to chemoradiation. There was no delay in chemoradiation, so you could give the full dose of standard chemoradiation. The second finding was that we looked at the T-cell clones in the patient’s peripheral blood and tumors and we found that patients who received chemoradiation had an expansion of T-cell clonality. They were new novel clones as opposed to just tumor-associated clones.

Reference

Mayadev J, Zamarin D, Deng W, et al. Safety and immunogenicity of anti PD-L1 (Atezolizumab) given as an immune primer or concurrently with extended field chemoradiotherapy for node positive locally advanced cervical cancer: an NRG Oncology trial. Presented at: 2022 SGO Annual Meeting on Women’s Cancer; March 18-21, 2022; Phoenix, Arizona.