ABSTRACT
Over the past decade, substantial advances have been made in the individualization of therapeutic strategies for metastatic colorectal cancer (mCRC). Treatment strategies have been developed and classified according to their molecular and genetic characteristics based on predictive biomarkers such as microsatellite instability, RAS and BRAF mutations, HER2 amplification, or NTRK fusions. As molecular and genetic predictive tests are routinely performed, new challenges for mCRC treatment strategies are allowed. For patients responding to anti-epithelial growth factor receptor treatments, expanded biomarkers panels enable customized treatment to be selected and the optimal treatment can be determined. Patients with mCRC with the BRAFV600E mutation who did not have effective targeted treatments have effective therapeutic options. Attractive but rare targets, such as HER2 amplification and NTRK fusions, could be a breakthrough and the use of immune checkpoint inhibitors in patients with mismatch repair deficiency/microsatellite instability is the striking revolution. In this review, we summarize the current landscape of targeted therapies for mCRC patients, with a focus on new developments for epithelial growth factor receptor blockade and emerging biomarkers.
ABSTRACT
Over the past decade, substantial advances have been made in the individualization of therapeutic strategies for metastatic colorectal cancer (mCRC). Treatment strategies have been developed and classified according to their molecular and genetic characteristics based on predictive biomarkers such as microsatellite instability, RAS and BRAF mutations, HER2 amplification, or NTRK fusions. As molecular and genetic predictive tests are routinely performed, new challenges for mCRC treatment strategies are allowed. For patients responding to anti-epithelial growth factor receptor treatments, expanded biomarkers panels enable customized treatment to be selected and the optimal treatment can be determined. Patients with mCRC with the BRAFV600E mutation who did not have effective targeted treatments have effective therapeutic options. Attractive but rare targets, such as HER2 amplification and NTRK fusions, could be a breakthrough and the use of immune checkpoint inhibitors in patients with mismatch repair deficiency/microsatellite instability is the striking revolution. In this review, we summarize the current landscape of targeted therapies for mCRC patients, with a focus on new developments for epithelial growth factor receptor blockade and emerging biomarkers.
ABSTRACT
PURPOSE: The incidence of gastrointestinal stromal tumors (GISTs) harboring platelet-derived growth factor receptor alpha (PDGFRA) mutations is low, therefore further investigation of the efficacy of imatinib in this subgroup was needed. MATERIALS AND METHODS: Patients with PDGFRA-mutant GISTs who received imatinib as primary therapy for advanced disease between January 2000 and June 2012 were identified from the GIST registry of Asan Medical Center, Seoul, Korea. RESULTS: KIT and PDGFRA genotyping in 823 patients identified 18 patients (2%) with PDGFRA mutations who were treated with first-line imatinib. Exon 18 D842V substitution, non-D842V exon 18 mutations, and exon 12 mutations were detected in nine (50%), four (22%), and five (28%) patients, respectively. Objective response rate differed significantly between patients with the D842V mutation and those with non-D842V mutations (0% [0/5] vs. 71% [5/7], p=0.03). In all patients, median progression-free survival (PFS) and overall survival (OS) was 24.8 months (95% confidence interval [CI], 0.0 to 57.2) and 51.2 months (95% CI, 37.1 to 65.3), respectively. Significantly, poorer PFS was observed for patients with D842V-mutant GISTs than those with non-D842V PDGFRA-mutant GISTs: median 3.8 months (95% CI, 1.4 to 6.3) versus 29.5 months (95% CI, 18.3 to 40.7) (p < 0.001). Patients with the D842V mutation had poorer OS than those with non-D842V PDGFRA mutations: median 25.2 months (95% CI, 12.7 to 37.8) versus 59.8 months (95% CI, 43.0 to 76.5) (p=0.02). CONCLUSION: Imatinib is active against non-D842V PDGFRA-mutant GISTs, whereas GISTs harboring the D842V mutation are primarily resistant to imatinib.
Subject(s)
Humans , Disease-Free Survival , Exons , Gastrointestinal Stromal Tumors , Incidence , Korea , Platelet-Derived Growth Factor , Receptors, Platelet-Derived Growth Factor , SeoulABSTRACT
BACKGROUND: Abbreviated chemotherapy followed by radiotherapy or full cycles of chemotherapy is recommended as a standard treatment for limited-stage (LS) diffuse large B-cell lymphoma (DLBCL). After complete resection of tumors, however, Burkitt and childhood B-cell Non-Hodgkin lymphoma show favorable outcomes, even after abbreviated chemotherapy of only 2 or 3 cycles. We investigated the effectiveness of abbreviated chemotherapy in patients with LS DLBCL after complete tumor resection. METHODS: We retrospectively reviewed 18 patients with LS DLBCL who underwent complete tumor resection followed by either 3 or 4 cycles of chemotherapy between March 2002 and May 2010. RESULTS: With a median follow-up period of 57.9 months (range, 31.8-130.2 months), no patients experienced disease relapse or progression; however, 1 patient experienced secondary acute myeloid leukemia during follow-up. The 5-year progression-free survival rate and overall survival rate were 93.3% and 94.1%, respectively. CONCLUSION: These results warrant further investigation into abbreviated chemotherapy as an alternative treatment for patients who have undergone complete resection of LS DLBCL.