Highlights of This Issue

Abstract

The FGFR pathway is thought to drive oncogenic progression of many tumor types. Bahleda and colleagues report on the results of a first-in-human phase I trial of erdafitinib (JNJ-42756493), a potent, oral pan-FGFR tyrosine kinase inhibitor, conducted on patients with advanced-stage disease with known genetic activation of the FGFR pathway. This agent was well-tolerated and showed promising efficacy, especially in urothelial carcinoma and cholangiocarcinoma patients with FGFR alterations. These results have the potential to influence future treatment of patients with FGFR positive tumors.Myelofibrosis is morphologically characterized by the presence of atypical megakaryocytes and bone marrow fibrosis. To determine whether elimination of these abnormal megakaryocytes has therapeutic benefit for myelofibrosis patients, Gangat and colleagues conducted a phase 1 study of alisertib, an aurora kinase A inhibitor and megakaryocyte differentiation agent. Alisertib was well-tolerated and provided a modest clinical benefit for spleen size and symptom burden. Moreover, alisertib normalized megakaryocyte morphology and reduced fibrosis in a substantial number of patients. This study underscores the role of megakaryocytes in myelofibrosis and highlights the feasibility of targeting this lineage in this disease.Cancer vaccines have long been considered a promising tool for cancer therapy. However, many potential vaccines have been ineffective in clinical trials, in part due to the immunosuppressive cancer microenvironment. In a phase I trial, Gatti-Mays and colleagues examined BN-CV301, a modified cancer vaccine expressing MUC1 and CEA tumor antigens, as well as costimulatory molecules. Treatment-related adverse events were relatively minor. Patients with mutant KRAS responded particularly well to this regimen – five out of six patients showed either a partial response or stable disease after BN-CV301 vaccination. This improved vaccine shows promise for further clinical evaluation.Pancreatic ductal adenocarcinoma is a highly lethal cancer due, in part, to a high rate of recurrence. Groot and colleagues developed and validated an assay to detect KRAS hotspot mutations in circulating tumor DNA (ctDNA) in a CLIA laboratory setting. Detection of mutant KRAS in ctDNA at the time of surgery was associated with a greater risk of recurrence, while rising mutant KRAS levels in ctDNA provided an early prediction of recurrence. In several instances, the detection of mutant KRAS in ctDNA outperformed the measurement of CA 19-9 in serum. This liquid biopsy test for mutant KRAS shows great promise for monitoring disease in pancreatic cancer patients, potentially leading to earlier intervention.