An exosome-based liquid biopsy predicts depth of response and survival outcomes to cetuximab and panitumumab in metastatic colorectal cancer: The EXONERATE Study.

PURPOSE EXONERATE (EXOsome and cell-free micro-RNAs of anti-EGFR ResistAnce) was an open-label, biomarker interventional study designed to develop, test, and validate a liquid biopsy predictive of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for first-line EGFR inhibitors in metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Patients with newly diagnosed RAS-WT, chemotherapy-naïve mCRC, both right- and left-sided, were enrolled in 2-nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The primary endpoint was 12-month PFS, which was hierarchically tested in left- and right-sided mCRC to predict PFS, OS, and ORR.

CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer.

Purpose: We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor ()-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status.

Methods: Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR).

Osimertinib with or without Chemotherapy in -Mutated Advanced NSCLC.

Background: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is selective for EGFR-TKI-sensitizing and T790M resistance mutations. Evidence suggests that the addition of chemotherapy may extend the benefits of EGFR-TKI therapy.

Methods: In this phase 3, international, open-label trial, we randomly assigned in a 1:1 ratio patients with -mutated (exon 19 deletion or L858R mutation) advanced non-small-cell lung cancer (NSCLC) who had not previously received treatment for advanced disease to receive osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg per square meter of body-surface area] plus either cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or to receive osimertinib monotherapy (80 mg once daily).

The EMT factor ZEB1 paradoxically inhibits EMT in BRAF-mutant carcinomas.

Despite being in the same pathway, mutations of KRAS and BRAF in colorectal carcinomas (CRCs) determine distinct progression courses. ZEB1 induces an epithelial-to-mesenchymal transition (EMT) and is associated with worse progression in most carcinomas. Using samples from patients with CRC, mouse models of KrasG12D and BrafV600E CRC, and a Zeb1-deficient mouse, we show that ZEB1 had opposite functions in KRAS- and BRAF-mutant CRCs.