Atezolizumab Plus Chemoradiation Is Safe in Node+, Locally Advanced Cervical Cancer

Adding atezolizumab (Tecentriq) prior to concurrent chemoradiation (CRT) appears safe and showed immune modulating activity for patients with node-positive, locally advanced cervical cancer, according to findings from the phase 1/1b trials (NRG-GY017; NCT03738228) presented during the Society for Gynecologic Oncology’s (SGO) Annual Meeting on Women’s Cancer in March 2022.¹

Of the 36 eligible patients in the study, 75% completed all of the study treatment. Among these patients, thirty patients were evaluable for DLTs. Only 3 patients exhibited DLTs.

“The goal of NRG-GY017 was to investigate peripheral blood T cell receptor (TCR) clonal expansion in response to chemoradiation and immunotherapy, and to establish the safety and efficacy of atezolizumab (anti PDL-1) immunotherapy as a primer to CRT combined with atezolizumab. This trial gives insight into the immunological basis for therapy response. These results allow future research to consider immunotherapy and treatment sequencing in larger scale trials as a way of improving outcomes for this high-risk population of women,” stated Jyoti Mayadev, MD, of the University of California, San Diego, and the lead author of the NRG-GY017 abstract.

According to Mayadev et al, there is a lack of research around the use and sequencing of immunotherapy and chemoradiation therapy in node-positive cervival cancer. Therefore, there is a need for translational research thay explores the mechanisms of response and resistance to immunotherapy in advanced cervical cancer. With this rationale, patients with histological confirmed, newly-diagnosed, advanced cervical cancer were enrolled, including patients with squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma. All patients had FIGO 2009 clinical stages IB2/IIA with positive para-aortic nodes, or FIGO 2009 clinical stages IIB/IIIB/IVA with positive pelvic or para-aortic lymph nodes, and the study excluded patients who had a prior hysterectomy or lymph node dissection.²

Investigators randomly assigned patients to either the treatment arm A (n = 16), where patients received 3 doses of atezolizumab, one prior to CRT and two doses during CRT, or to treatment arm B (n = 14), where patients received all 3 doses of atezolizumab during CRT treatment. Tumor biopsies were taken before and during treatment, peripheral blood was collected, and dose limiting toxicities (DLT) were assessed for all eligible patients.Secondary end points included toxicity and the predictive value of T-cell repertoire parameters for clinical outcomes.

The median follow-up was 20 months. No patients evaluable from arm A (n = 16) exhibited DLTs, and 3 of the 14 evaluable patients on arm B reported to have a DLT (8%).

Both peripheral blood T-cell receptor (TCR) clonal expansion and expansion of tumor-associated T-cell clones increased between the start of treatment and day 21 of CRT in arm A (P =.0001) and arm B (P = 001). Patients with higher pre-treatment TCR diversity had increased likelihood of complete pathologic response in on-treatment biopsy (P =.049).

Overall, 3 patients on treatment arm A and 10 patients on treatment arm B experienced a grade 3 or higher treatment-related adverse events with only 1 being immune related.

More data being collected in follow up will be reported at a later date.

_Reference

_{1. NRG oncology trial indicates using atezolizumab with chemoradiation is safe and demonstrates signs of immune activation in women with cervical cancer. Press release. NRG Oncology. March 18, 2022. Accessed March 22, 2022. https://bit.ly/3iszwG1}

_{2. Mayadev J, Zamarin D, Deng W, et al. Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer [published correction appears in Int J Gynecol Cancer. 2020 Jul;30(7):1084] [published correction appears in Int J Gynecol Cancer. 2020 Aug;30(8):1266]. Int J Gynecol Cancer. 2020;30(5):701-704. doi:10.1136/ijgc-2019-001012}