The US FDA has approved Guardant360 CDx as a companion diagnostic for Veppanu (vepdegestrant), the PROTAC estrogen receptor degrader jointly developed by Arvinas and Pfizer, in patients with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. The liquid biopsy test, developed by Guardant Health, detects ESR1 mutations from a blood draw and is intended to identify patients eligible for treatment with Veppanu following progression on at least one prior line of endocrine therapy.
The approval marks the third ESR1-related companion diagnostic designation for Guardant360 CDx and its 26th companion diagnostic indication across solid tumor types. Veppanu, which received FDA approval as a first-in-class PROTAC heterobifunctional protein degrader in oncology, is indicated for adults whose tumors harbor ESR1 mutations as detected by an FDA-authorized test, making the companion diagnostic designation a functional prerequisite for patient selection in clinical practice.
ESR1 mutations are acquired resistance alterations that emerge in a substantial proportion of patients treated with aromatase inhibitors, particularly in combination with CDK4/6 inhibitors. Estimates cited in the approval context suggest that 40 to 50% of patients progressing on CDK4/6 inhibitor-based endocrine therapy may carry ESR1 mutations detectable in circulating tumor DNA. Because these mutations arise under selective pressure during treatment rather than being present at diagnosis, blood-based testing at the point of progression offers a practical advantage over tissue re-biopsy in capturing the current mutational state of the tumor.
The companion diagnostic approval situates Guardant360 CDx within a competitive landscape for ESR1 mutation testing in advanced breast cancer. The platform had previously received companion diagnostic approvals linked to elacestrant (Orserdu) and imlunestrant (Inluriyo), the two oral selective estrogen receptor degraders that preceded Veppanu in gaining FDA approval for ESR1-mutated ER-positive, HER2-negative metastatic breast cancer. Elacestrant was approved in January 2023, imlunestrant in September 2025, and Veppanu in May 2026, compressing into roughly three years a transformation of the post-CDK4/6 inhibitor endocrine therapy landscape from a single injectable option in fulvestrant to three orally or mechanistically distinct agents.
For Guardant Health, the approval extends the clinical utility of a platform that the company describes as covering more than 300 million lives through Medicare and commercial payer agreements. The test detects multiple genomic alterations across solid tumors and has accumulated companion diagnostic indications spanning non-small cell lung cancer, breast cancer, and colorectal cancer. The ESR1 mutation context is notable because it represents a biomarker that is dynamic rather than germline or constitutive, emerging during the course of metastatic disease and therefore requiring testing at or near the point of treatment selection rather than at initial diagnosis.