March 25, 2022
2 min read
Mayadev J, et al. Abstract 24. Presented at: Society of Gynecologic Oncology 2022 Annual Meeting on Women’s Cancer (hybrid meeting); March 18-21, 2022; Phoenix.
Genentech, NCI and NIH supported the study. Mayadev reports no relevant financial disclosures. Please see the abstract for all researchers’ relevant financial disclosures.
Atezolizumab administered before and during chemoradiation appeared safe and demonstrated immune-modulating activity among women with node-positive locally advanced cervical cancer, according to study results.
Researchers presented the study findings in a plenary session during the Society of Gynecologic Oncology 2022 Annual Meeting on Women’s Cancer.
Rationale and methods
The goal of combining immunotherapy with chemoradiation is to improve outcomes for women with node-positive cervical cancer. However, the optimal sequencing of the combination is not well-known, according to study background.
“The goal of [this trial] was to investigate peripheral blood T-cell receptor clonal expansion in response to chemoradiation and immunotherapy, and to establish the safety and efficacy of atezolizumab [Tecentriq, Genentech], an anti-PD-L1 [therapy], as a primer to chemoradiation combined with atezolizumab,” Jyoti Mayadev, MD, lead author and radiation oncologist at University of California, San Diego, said in a press release. “This trial gives us 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.”
The phase 1/1b trial included 36 women (median age, 48 years) with locally advanced cervical cancer with positive lymph nodes randomly assigned to either one dose of 1,200 mg atezolizumab before and two doses during chemoradiation (arm A) or to all three doses during chemoradiation (arm B).
Researchers obtained tumor biopsies before and during treatment, collected peripheral blood and assessed dose-limiting toxicities for all women.
Determining the best treatment sequence to achieve immune activation served as the primary objective, and secondary objectives included toxicity and the predictive value of T-cell repertoire parameters for clinical outcomes.
Overall, 75% of women completed the study protocol, with median follow-up of 20 months.
Among the 30 women evaluable for dose-limiting toxicities, the 16 in arm A had none compared with three (8%) of the 14 in arm B.
Three women in arm A and 10 women in arm B experienced grade 3 or higher treatment-related adverse events, including one immune-related event.
Between the initiation of treatment and day 21 of chemoradiation, researchers observed an increase in peripheral blood T-cell receptor clonal expansion and expansion of tumor-associated T-cell clones in arm A (P = .0001) and in arm B (P = .001).
Women with increased pretreatment T-cell receptor diversity more frequently experienced complete pathologic response in on-treatment biopsy (P = .049).
The overall cohort had a 1-year DFS rate of 72%.
Correlations between treatment schedule, T-cell repertoire parameters and clinical outcomes are expected to be reported at a future date as the data mature, according to Mayadev and colleagues.