ctDNA Helped Predict Response, Survival After Durvalumab in Lung, Bladder Cancer

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Analyzing ctDNA following drug treatment could help identify nonresponders to immunotherapy.
Analyzing ctDNA following drug treatment could help identify nonresponders to immunotherapy.

A decrease in the variant allele frequencies (VAF) of somatic mutations found in circulating tumor DNA (ctDNA) during treatment with durvalumab was associated with improved survival in patients with lung and urothelial cancer, according to a recent study published in Clinical Cancer Research.1

“This early change may be a useful and noninvasive way to predict long-term benefit from immunotherapy, opening up unique opportunities to support decision making in indications where image-based response analysis may not be reliable, and to enable early treatment decisions before availability of radiographic response,” the researchers wrote. 

The study consisted of a discovery cohort and 2 validation cohorts. VAF of somatic mutations in 73 genes were assessed in ctDNA first in a discovery cohort of 28 patients with non-small cell lung cancer (NSCLC) and then validated in 72 patients with EGFR-wild-type NSCLC and 29 patients with urothelial cancer. 

In the discovery cohort, at least 1 somatic variant was observed in 96% of patients. In the validation cohorts, at least 1 was found in 100% of patients with urothelial cancer and 94% of patients with NSCLC. According to the researchers, this suggested that the method used “has sensitivity required for ddetecting ctDNA in most patients with these advanced cancers.”

The changes in VAF preceded radiographic responses, and the patients with reduction in VAF at 6 weeks had significantly greater reduction in tumor volume, with longer progression-free survival and overall survival. 

Those patients with NSCLC in the discovery cohort with mean change in VAF (dVAF) of 0 or greater had shorter progression-free survival compared with patients with dVAF of less than 0 (median PFS 1.45 vs. 13.7 months). The median overall survival was also shorter in patients with dVAF of 0 or greater compared with dVAF of less than 0 (9.07 months vs 28.13 months).

According to the researchers, prospective studies are needed to validate these findings. 

Disclosure: The original study covered in this article was funded by MedImmune/AstraZeneca. Publication costs for the original article were defrayed in part by the payment of page charges and thus, this article is marked as an advertisement in that journal. For more information about these disclosures, please refer to the original article.

Reference

  1. Raja R, Kuziora M, Brohawn PZ, et al. Early reduction in ctDNA predicts survival in patients with lung and bladder cancer treated with durvalumab [published online August 9, 2018]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-18-0386

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