Stintzing S, von der Heyde E, Wierecky Jan, et al. Background: BRAF V600E-mutant metastatic colorectal cancer (mCRC) is associated with a poor prognosis and limited clinical data. Based on results from the BEACON CRC trial, targeted treatment with encorafenib plus cetuximab (E+C) is available as a standard of care for these patients (pts) after prior systemic...
Author: s.mengoni@pensiero.it
Microsatellite instability, mismatch repair, and TMB as predictive biomarkers for immune checkpoint inhibitor effectiveness in real-world patients with mCRC
Ellis H, Klempner S, Quintanilha J, et al. Background: The KEYNOTE-177 randomized controlled trial demonstrated that mCRC patients with MSI high (MSI-H) and/or deficient MMR (dMMR) have better outcomes on first-line ICI than chemotherapy. This study aimed to evaluate MSI by next-generation sequencing (NGS) as a predictive biomarker of ICI effectiveness in real-world settings, and compare...
Effectiveness and safety of encorafenib-cetuximab in BRAFV600E mCRC: Confidence study
Fernandez Montes A, Elez E, Graña B, et al. Background: BRAFV600E mutant metastatic colorectal cancer (mCRC) has a poor prognosis. The BEACON trial demonstrated an improvement in tumor response, overall survival (OS), and progression-free survival (PFS) when administering encorafenib-cetuximab (EC) to patients (pts) who progressed after 1 or 2 therapy lines. This study provides a retrospective analysis...
mCRC, da ASCO GI nuove evidenze e importanti conferme
Interessanti nuove evidenze dall’ultima edizione dell’ASCO Gastrointestinal Cancers Symposium per quanto concerne il trattamento del tumore del colon-retto. Nel setting di malattia avanzata con mutazione di BRAFV600E si conferma quale standard of care la combinazione encorafenib + cetuximab. Numerosi studi, inoltre, mostrano ulteriori significativi vantaggi legati alle associazioni con immunoterapia. L’overview di Lisa Salvatore, UOC...
SEAMARK: Randomized phase 2 study of pembrolizumab + encorafenib + cetuximab vs pembrolizumab alone for first-line treatment of BRAF V600E–mutant MSI-H/mismatch repair deficient mCRC
Kopetz S, Bekaii-Saab TS, Yoshino T, et al. Background: Among patients with MSI-H/dMMR CRC, BRAF mutations occur in approximately 30%. MSI-H/dMMR and BRAF mutations are both associated with poor prognosis; in patients who have both biomarkers, poor prognosis is thought to be driven by the BRAF mutation. Pembrolizumab is indicated for the treatment of patients with MSI-H/dMMR unresectable or metastatic CRC (mCRC)....
Randomized phase II trial of encorafenib and cetuximab with or without nivolumab for patients with previously treated, microsatellite stable, BRAFV600E metastatic and/or unresectable colorectal cancer: SWOG S2107
Morris VK, Guthrie KA, Kopetz S, et al. Background: Patients with microsatellite stable (MSS), BRAFV600E metastatic colorectal cancer (mCRC) experience poor survival outcomes. Treatment with the BRAF inhibitor encorafenib (E) and anti-EGFR antibody cetuximab (C) is an approved treatment combination, with a reported overall response rate (ORR) of 20% and median progression-free survival (PFS) of 4.1 months. Anti-PD-1...
Nuove linee guida per il trattamento del tumore del colon-retto
Le nuove linee guida per il trattamento del tumore del colon-retto danno indicazioni molto dettagliate sull’importanza di eseguire un’approfondita valutazione molecolare della neoplasia al fine di adottare protocolli ad hoc che ottimizzino l’efficacia del trattamento. Questo vale per tutte le fasi di malattia ed è tanto più è rilevante nel caso di patologia avanzata o...
TRIDENTE trial: a phase II study of rechallenge with encorafenib, binimetinib, and cetuximab in patients with RAS wild-type/BRAF V600E–mutant mCRC
Kotani D, Kagawa Y, Matsubara Y, et al. Background: The BEACON CRC trial demonstrated survival benefit of combination therapy with encorafenib (ENCO) + cetuximab (CET) +/- binimetinib (BINI) in patients with RAS wild-type (WT)/BRAF V600E mutant metastatic colorectal cancer (mCRC). However, prognosis of those patients still be poor after the refractoriness to the BEACON combination therapy. One of resistant...
A single-arm, phase II study of autophagy modulation using hydroxychloroquine in addition to encorafenib and cetuximab or panitumumab in metastatic BRAF-mutated colorectal cancer refractory to standard therapy
Vakkalagadda C, Mukit S, Kocherginsky M, et al. Background: BRAF mutations drive 5-10% of colon cancers. BRAF + EGFR inhibition with encorafenib + cetuximab is standard second-line therapy, per the BEACON trial, but responses are short-lived. Autophagy induction is implicated as a mechanism for this acquired resistance to therapy. Preclinical models have shown that BRAF inhibition...