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Comparison of tissue genotyping (TG) vs circulating tumor DNA (ctDNA) for selection of matched therapy and impact on clinical outcomes among patients with metastatic breast cancer (MBC).
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2018
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Breast OncologyCancer PathologyCancer ManagementPathologyTumor BiologyCancer DetectionMatched TherapyClinical OutcomesMolecular DiagnosticsRadiation OncologyMolecular OncologyCancer ResearchRadiologyHealth SciencesMetastatic Breast CancerCtdna TestingMedicineCancer TreatmentCancer GeneticsMolecular MedicineCtdna PatientsCancer GenomicsBreast CancerOncology
1020 Background: Oncogenic mutations are attractive targets for targeted therapies, but the clinical impact is unclear. We evaluated the impact of TG or ctDNA on the selection of matched therapy and clinical outcomes in MBC patients. Methods: MBC patients with TG (Next Generation Sequencing/NGS, institutional platform) or ctDNA (NGS, Guardant360) at Massachusetts General Hospital between 1/2016-12/2017 were identified. A review of records to identify tumor subtype, demographics, treatment, outcomes, and TG or ctDNA results was performed. Associations between genomic results and the selection of matched therapy targeted to an actionable mutation, progression free survival, and overall survival (OS) were determined. Results: Among 252 patients with ctDNA testing, 232 (92%) had detectable mutations. Of those 232 cases, 196 (84%) had actionable mutations and 86 patients with actionable mutations received matched therapy with agents including CDK 4/6, mTOR, PI3K, AKT, PARP, androgen receptor, and FGFR inhibitors, SERDs, HER2 directed therapy, and DNA damaging chemotherapy. Among 118 patients with TG, 90 (76%) had detectable mutations. Of those 90 cases, 59 (66%) were actionable and 13 patients with actionable mutations received matched therapy with agents including mTOR, PI3K, or AKT inhibitors, or SERDs. There were significantly more actionable mutations detectable by ctDNA vs TG (84.5% vs 65.6%, p < 0.0005) and a significantly higher proportion of patients with ctDNA vs TG received matched therapy (46.7% vs 27.7%, p = 0.018). On multivariate Cox regression analysis adjusted for tumor subtype in ctDNA patients, OS was significantly better for patients with matched therapy vs those with unmatched therapy (HR 0.45, 95% CI 0.25-0.80, p = 0.007). Additional survival analyses will be presented at the meeting. Conclusions: ctDNA testing resulted in higher detection and greater application of matched therapy as compared with TG. Patients who had matched therapy based on ctDNA results had better OS compared to those with unmatched therapy post-ctDNA testing. These novel findings require confirmation in additional studies.