Jyoti Mayadev, MD, Provides Perspective on Atezolizumab in Locally Advanced Cervical Cancer

At The Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer, Jyoti S. Mayadev, MD, presented on her research in the randomized phase 1 NRG-GY017 trial (NCT03738228) looking at atezolizumab (Tecentriq) with either an immune primer or in combination with extended-field chemoradiation for patients with locally advanced, node-positive cervical cancer.

Results presented at the meeting showed promising progression-free survival (PFS) outcomes, few dose-limiting toxicities (DLTs), and evidence of clonal T-cell expansion in tumors and peripheral blood, providing a promising outlook for use of the PD-L1 inhibitor in this setting going forward.

“NRG-GY017 with concurrent atezolizumab or priming atezolizumab with chemoradiation was safe and very well tolerated. We think that the T-cell clonality expansion observed in tumors and the peripheral blood was irrespective of sequencing, but it’s quite interesting, and we hope to do more studies looking at this and correlating this [approach] with PFS and overall survival,” Mayadev, 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, said during the presentation of the data.

To learn more about how these results may influence the standard of care in locally advanced cervical cancer, CancerNetwork^® sat down with Mayadev to talk about the outcomes of the trial and what she hopes will come of it going forward.

CancerNetwork^®: What was the rationale behind examining atezolizumab as an immune primer or concurrently with chemoradiotherapy in node-positive cervical cancer?

Mayadev: 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 versus the concurrent [therapy] arm—to determine if that would be a signal for response and overall survival.

What were some of the key highlights of this research?

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 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.

Were there any other findings from the research that you wanted to highlight?

We are looking forward to analyzing the T-cell clonality data and the new clones in terms of correlating them to PFS. The other thing we looked at was response in terms of the biopsies during chemoradiation. We hope to look at [biopsies of long-term responders] showing a complete response to their T-cell clones and the immune microenvironment to correlate those with PFS.

Where do you see future research efforts being focused from here?

With cervical cancer, we need research focus and efforts [toward] patients who recur after standard chemoradiation. The landscape of cervical cancer in the locally advanced setting is changing and shifting and we'll see more immunotherapy used with chemoradiation in the future.

What do you hope your colleagues took away from the presentation?

That combining immunotherapy with chemoradiation was safe and showed signals of efficacy compared with historical controls. There’s much translational work that we still need to do in terms of the immune microenvironment looking at predictive and prognostic biomarkers to help predict who's a responder and [for whom] we need to potentially look back at our standard treatments to modify them.

Were there any other presentations at SGO 2022 that you’re excited about?

We’re always looking at new novel agents for cervical cancer [as well as] patient-reported outcomes. I’m looking forward to hearing the [patient-reported outcomes from the KEYNOTE-826 trial (NCT03635567)] and trying to make life longer with a better quality of life for those with locally advanced or recurrent metastatic cervical cancer.

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.