Dr Mayadev on the Prognostic Value of ctDNA in Locally Advanced Cervical Cancer

"Using this ultra-sensitive [ctDNA] assay was both predictive and prognostic for locally advanced cervical cancer, and patients who had a positive ctDNA after their treatment cycle of chemotherapy, radiation, and durvalumab or placebo did worse in terms of progression-free survival and overall survival."

Jyoti Mayadev, MD, a professor, the assistant vice-chair of Developmental Therapeutics, and section chief of Gynecologic Oncology at UC San Diego Health, discussed the prognostic and predictive significance of circulating tumor DNA (ctDNA) dynamics in patients with locally advanced cervical cancer (LACC), based on a preplanned exploratory analysis of the phase 3 CALLA trial (NCT03830866), which evaluated chemoradiotherapy (CRT) with or without durvalumab (Imfinzi).

This analysis utilized an ultrasensitive, tumor-informed ctDNA assay to assess baseline ctDNA levels and molecular response following treatment. ctDNA was detectable at baseline in 99% of patients across both treatment arms. At day 1 of cycle 6, the ctDNA-positivity rates were 36% in the CRT plus placebo arm (n = 24/66) vs 23% in the durvalumab plus CRT arm (n = 15/64)

Patients with high baseline ctDNA levels experienced poorer progression-free survival (PFS) and overall survival (OS), regardless of whether they received the durvalumab regimen (HR, 0.04; 95% CI, 0.01-0.16) or the placebo regimen (HR, 0.04; 95% CI, 0.01-0.17).

Continued ctDNA positivity at cycle 3 was also independently associated with worse outcomes. Among those with persistent ctDNA positivity, 68% of patients experienced disease progression or relapse. In contrast, in patients whose ctDNA became undetectable at cycle 3, 83% had not experienced disease progression.

Mayadev noted that the prognostic value of ctDNA was further supported in a subset of patients with PD-L1 tumor area positivity of at least 20%, where the reduction in ctDNA detection was more pronounced in the durvalumab-treated cohort. Although exploratory, these findings suggest a potential predictive signal for immunotherapy benefit in this biomarker-defined subgroup. Importantly, the assay was able to identify molecular relapse up to 497 days before radiographic progression, underscoring its potential as an early indicator of treatment failure, she said.

These data support the integration of ultrasensitive ctDNA monitoring into clinical management of locally advanced cervical cancer, Mayadev explained. The ability to identify high-risk patients based on post-treatment ctDNA status could inform tailored surveillance strategies and early intervention approaches. Although additional validation is needed, the findings highlight the utility of ctDNA as a noninvasive, real-time biomarker for disease monitoring in cervical cancer, she concluded.