Durable benefit from poly(ADP-ribose) polymerase inhibitors in metastatic prostate cancer in routine practice: biomarker associations and implications for optimal clinical next-generation sequencing testing.

Background: Controlled trials have consistently demonstrated the efficacy of poly(ADP-ribose) polymerase inhibitors (PARPis) in patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1 or BRCA2 alterations (BRCAalt). However, the reported efficacy of PARPi for alterations in other homologous recombination repair (HRR) genes is less consistent. We sought to evaluate the routine practice effectiveness of PARPi between and within these groups.

Measurement of ctDNA Tumor Fraction Identifies Informative Negative Liquid Biopsy Results and Informs Value of Tissue Confirmation.

Purpose: Liquid biopsy (LBx) for tumor profiling is increasingly used, but concerns remain regarding negative results. A lack of results may truly reflect tumor genomics, or it may be a false negative that would be clarified by tissue testing. A method of distinguishing between these scenarios could help clarify when follow-on tissue testing is valuable.

Liquid Biopsy of Lung Cancer Before Pathological Diagnosis Is Associated With Shorter Time to Treatment.

Purpose: Studies have investigated the early use of liquid biopsy (LBx) during the diagnostic workup of patients presenting with clinical evidence of advanced lung cancer, but real-world adoption and impact has not been characterized. The aim of this study was to determine whether the use of LBx before diagnosis (Dx; LBx-Dx) enables timely comprehensive genomic profiling (CGP) and shortens time until treatment initiation for advanced non-small-cell lung cancer (aNSCLC).

Materials And Methods: This study used the Flatiron Health-Foundation Medicine electronic health record-derived deidentified clinicogenomic database of patients with aNSCLC from approximately 280 US cancer clinics.

Homologous Recombination Deficiency Landscape of Breast Cancers and Real-World Effectiveness of Poly ADP-Ribose Polymerase Inhibitors in Patients With Somatic /, Germline , or Homologous Recombination Deficiency Signature.

Purpose: Poly ADP-ribose polymerase inhibitors (PARPi) are approved for patients with human epidermal growth factor receptor 2-negative metastatic breast cancer (mBC) and germline pathogenic/likely pathogenic variant (hereafter mutation) in the / genes (g); however, clinical benefit has also been demonstrated in mBC with somatic / mutations (s) or germline mutations (g). This study aims to describe the genomic landscape of homologous recombination repair (HRR) gene alterations in mBC and assess PARPi treatment outcomes for patients with g compared with other HRR genes and by status of a novel homologous recombination deficiency signature (HRDsig).

Methods: A real-world (RW) clinico-genomic database (CGDB) of comprehensive genomic profiling (CGP) linked to deidentified, electronic health record-derived clinical data was used.

Real-World Genomic Profile of EGFR Second-Site Mutations and Other Osimertinib Resistance Mechanisms and Clinical Landscape of NSCLC Post-Osimertinib.

Introduction: The emergence of osimertinib as standard of care for EGFR-mutant NSCLC has renewed the need to understand and overcome drug resistance. We sought to understand the genomics and real-world treatment landscape of NSCLC with EGFR C797S and other on- and off-target resistance mechanisms.

Methods: Comprehensive genomic profiling (CGP) results from tissue or blood samples from 93,065 patients with NSCLC were queried for osimertinib EGFR second-site resistance mutations (ssEGFRms; C797, L718, G724, G796, L792).