Greg Andrew Durm

Targeting multiple angiogenic pathways simultaneously: experience with nintedanib in non-small-cell lung cancer

Angiogenesis plays a major role in the growth and progression of non-small-cell lung cancer (NSCLC), and there is increasing interest in the development of therapies that block this particular aspect of tumorigenesis. Bevacizumab was the first US FDA-approved inhibitor of angiogenesis after demonstrating improved progression-free survival and overall survival in combination with chemotherapy in treating NSCLC. However, the benefit of bevacizumab is only modest and transient as the tumors inevitably develop resistance to this particular treatment. Therefore, new therapies are being developed that attempt to inhibit angiogenesis through several different pathways. One promising new drug, nintedanib, is an oral triple angiokinase inhibitor that acts by blocking not only VEGFR, but also FGFR and PDGFR, which are involved in the development of resistance to bevacizumab. This article discusses the rationale for this approach and summarizes the clinical trial data on nintedanib, including the two most recent Phase III trials.

Second-Line Chemotherapy and Beyond for Non–Small Cell Lung Cancer

The landscape for the second- and third-line treatment of advanced non-small cell lung cancer has changed dramatically over the last two decades. Immunotherapeutic agents have become a preferred choice following progression on platinum-based first-line chemotherapy. However, there remains a role for cytotoxic chemotherapy and pemetrexed and docetaxel (with or without ramucirumab) are approved for single-agent use in the second-line setting. With the discovery of new genetic alterations and the development of novel targeted drugs, the treatment of advanced non-small cell lung cancer following progression on first-line therapy continues to become more complicated as new treatment algorithms evolve.

TMPRSS2-ERG Fusion in an Uncommon Presentation of Prostate Cancer

Patients with metastatic prostate cancer can present or relapse in peculiar fashion. Routine assessment of tumor pathology and immunohistochemistry can be diagnostic in many instances. However, some cases require more sophisticated testing to make the diagnosis. In this brief report, a patient with initially localized prostate cancer and undetectable prostate-specific antigen presented with a large mass in his sternum and mediastinal lymphadenopathy. The biopsy of the sternal mass was nonconclusive; hence, next generation sequencing was performed, showing transmembrane protease, serine 2 (TMPRSS2)-ETS gene fusion. TMPRSS2-ETS gene fusion appears to be specific and exclusive for prostate cancer and hence can be diagnostic, confirming the diagnosis of recurrent prostate cancer in this patient. When there is uncertainty regarding a diagnosis of prostate cancer, testing for TMPRSS2-ERG fusion by immunohistochemistry, fluorescence in situ hybridization, or DNA sequencing will result in the establishment of an accurate diagnosis.