Dr Mayadev on a ctDNA Analysis of the CALLA Trial in Cervical Cancer

“With our [study] looking at an ultrasensitive ctDNA assay, we’re starting to find blood-based biomarkers that will help [us] determine further therapy strategies, or if they even need further therapy after chemoradiation.”

Jyoti Mayadev, MD, a professor, the assistant vice-chair of Developmental Therapeutics, and section chief of Gynecologic Oncology at the University of California, San Diego Moores Cancer Center, discussed an analysis of the phase 3 CALLA trial (NCT03830866), which evaluated the value of circulating tumor DNA (ctDNA) as a prognostic biomarker for relapse and survival in patients with locally advanced cervical cancer.

CALLA was a global, randomized study that examined durvalumab (Imfinzi) plus chemoradiotherapy vs chemoradiotherapy alone in patients with locally advanced cervical cancer, Mayadev began. Although results from the study showed no difference in the primary end point of progression-free survival (PFS), investigators planned an exploratory analysis of efficacy outcomes by ultrasensitive ctDNA at baseline, after chemoradiation, and 3 months post chemoradiation, she added. The ctDNA assay used whole-genome sequencing, which allowed for a tumor-specific panel that examined ctDNA at 1 to 3 parts per million, she explained.

Findings from the exploratory analysis presented during the 2025 ASCO Annual Meeting demonstrated that patients with undetectable ctDNA at day 1 of cycle 3 in the combination arm (n = 60) experienced a significant PFS benefit compared with those who had detectable ctDNA (n = 33; HR, 0.23; 95% CI, 0.11-0.50). A PFS benefit in favor of the undetectable ctDNA (n = 56) vs detectable (n = 37) was also reported in the control arm (HR, 0.15; 95% CI, 0.07-0.33). A benefit was also observed in terms of overall survival (OS) in favor of the ctDNA-undetectable subgroup in the investigational (HR, 0.20; 95% CI, 0.09-0.47) and control (HR, 0.18; 95% CI, 0.08-0.38) arms.

These results represent the discovery of a potential blood-based biomarker that will not only inform strategies for additional treatment, but could help determine whether further therapy after chemoradiation is needed at all, Mayadev said. Treatment for patients with cervical cancer continues to shift towards more personalized approaches, she concluded.