The team therefore reviewed the ctDNA results from 80,911 treatment-naïve or previously treated patients with metastatic solid tumors who underwent Guardant360 (Guardant Health, Redwood City, California, USA) testing between July 2014 and June 2019.

“These data suggest that there may be a period in which MRD is detectable via ctDNA before overt, late breast cancer recurrences,” the investigators write.

More than half (56%) of patients were positive for ctDNA in samples taken either before or after treatment, and ctDNA was detected in 26% of all 363 longitudinal samples tested.

The researchers then looked at early ctDNA dynamics and found that there were significant reductions in VAF of 64.3% and 68.6% by day 15 of cycle 1 and day 1 of cycle 2, respectively.

Guru Sonpavde outlines the findings of their immunotherapy study supporting a potential role for longitudinal ctDNA profiling to identify suitable therapies for people with metastatic urothelial cancer. This independent video interview was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany

For ctDNA, the adjusted C-statistic to predict PFS was 0.68, while it was 0.85 for OS – these values were better than those for RECIST clinical response, at 0.61 and 0.68, respectively, said Romero.

There was also a significant correlation between elevated ctDNA in samples collected prior to initiating oncologic or surgical therapy and worse DFS (HR=3.30; five studies).

Further analysis showed a higher rate of ctDNA clearance among the 99 ctDNA-positive patients who were treated with atezolizumab than the 79 ctDNA-positive patients who received observation.

The researchers report that there was a high level of agreement between different ctDNA testing techniques (96–99%), and also high sensitivity for ctDNA digital PCR when compared with mutations identified in advanced breast cancer tissue biopsies, at 93% overall and 98% with concurrent biopsies.

In total, 85% (35/41) of ctDNA-negative patients showed pathologic downstaging and among patients initially ctDNA positive but with subsequent clearance the response rate was 53% (9/17), compared with 0% (0/8) among patients without ctDNA clearance.

They drew on a cohort of 93 patients from 12 Spanish institutions without sufficient tissue for genotyping, and found that 89% had detectable levels of ctDNA.

All patients with confirmed pseudoprogression had a favorable ctDNA profile, defined as undetectable ctDNA at baseline and during treatment or detectable ctDNA at baseline that became undetectable or decreased at least 10-fold within 12 weeks of treatment.

The study authors therefore investigated the utility of blood-derived ctDNA to evaluate the burden of mutations, noting that the noninvasive and inexpensive nature of a liquid biopsy may make their findings “clinically exploitable.”

However, he noted that more data are required to determine the impact of PD-L1 expression for adjuvant checkpoint inhibitor use, as well as to assess the importance of EGFR mutation status, the use of adjuvant chemotherapy and neoadjuvant therapies, and the application of ctDNA status as a biomarker.

Patients who were positive for ctDNA had significantly worse DDFS compared with their counterparts who were negative for ctDNA, at a median of 32.5 months versus unreached, and a hazard ratio (HR) of 2.99.

Bora Lim rounds up the breast cancer studies that caught her attention at the virtual 2020 ASCO Annual Meeting, including the MONALEESA pooled ctDNA analysis and the BYLieve trial (7:04).

Specifically, ctDNA genotyping identified driver mutations in an additional 252 patients, half of whom became eligible for targeted therapy, while the remainder were ruled out due to the detection of KRAS mutations.

. © 2019 Springer Healthcare part of the Springer Nature group Eur Urol 2019; doi:10.1016/j.eururo.2019.06.032 See also: ctDNA predicts relapse and response in bladder cancer Adjuvant radiotherapy may benefit locally advanced bladder cancer patients