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. 2020 Sep;1(9):873-881.
doi: 10.1038/s43018-020-0096-5. Epub 2020 Aug 3.

Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab

Scott V Bratman #  1   2   3 , S Y Cindy Yang #  1   3 , Marco A J Iafolla  3   4 , Zhihui Liu  3   5 , Aaron R Hansen  3   4 , Philippe L Bedard  3   4 , Stephanie Lheureux  3   4 , Anna Spreafico  3   4 , Albiruni Abdul Razak  3   4 , Svetlana Shchegrova  6 , Maggie Louie  6 , Paul Billings  6 , Bernhard Zimmermann  6 , Himanshu Sethi  6 , Alexey Aleshin  6 , Dax Torti  7 , Kayla Marsh  7 , Jenna Eagles  7 , Iulia Cirlan  3 , Youstina Hanna  3 , Derek L Clouthier  3 , Scott C Lien  3   8 , Pamela S Ohashi  3   8 , Wei Xu  3   5 , Lillian L Siu  9   10 , Trevor J Pugh  11   12   13
Affiliations

Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab

Scott V Bratman et al. Nat Cancer. 2020 Sep.

Abstract

Immune checkpoint blockade (ICB) provides clinical benefit to a subset of patients with cancer. However, existing biomarkers do not reliably predict treatment response across diverse cancer types. Limited data exist to show how serial circulating tumor DNA (ctDNA) testing may perform as a predictive biomarker in patients receiving ICB. We conducted a prospective phase II clinical trial to assess ctDNA in five distinct cohorts of patients with advanced solid tumors treated with pembrolizumab (NCT02644369). We applied bespoke ctDNA assays to 316 serial plasma samples obtained at baseline and every three cycles from 94 patients. Baseline ctDNA concentration correlated with progression-free survival, overall survival, clinical response and clinical benefit. This association became stronger when considering ctDNA kinetics during treatment. All 12 patients with ctDNA clearance during treatment were alive with median 25 months follow up. This study demonstrates the potential for broad clinical utility of ctDNA-based surveillance in patients treated with ICB.

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