Articles

Gene mutations or rearrangements in the tropomyosin receptor kinase (TRK) family of receptor tyrosine kinases are emerging as an important driver of cancer-cell growth in a wide range of cancers. Research has shown that neurotrophic receptor tyrosine kinase (NTRK) genes, which encode for TRK proteins, can fuse abnormally to other genes and enhance cell signals that support tumor growth. NTRK gene fusions are found in a variety of tumor types, including soft-tissue sarcoma, salivary gland cancer, infantile fibro­sarcoma, thyroid cancer, and lung cancer.

Febrile neutropenia is a serious complication of cancer chemotherapy that can require treatment delays and chemotherapy dose reductions, which compromise the efficacy of treatment. Among patients with cancer who are receiving chemotherapy, approximately 1% have febrile neutropenia. This condition affects patient morbidity and mortality and its clinical management requires significant healthcare resources.

Prostate cancer is the third most common type of cancer in the United States, after breast cancer and lung cancer. In 2018 alone, 164,690 individuals were diagnosed with prostate cancer, accounting for nearly 10% of all new cancer cases, and 29,430 deaths were attributed to the disease. Prostate cancer is most frequently diagnosed in men aged 65 to 74 years (median age, 66 years). More than 98% of patients with prostate cancer survive ≥5 years; however, the 5-year survival rate drops to 30% for patients with metastatic disease.

On May 3, 2019, the US Food and Drug Administration (FDA) approved ado-trastuzumab emtansine (Kadcyla; Genentech) for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Patients should be selected for treatment with this agent based on an FDA-approved companion diagnostic test (Ventana Medical System’s PATHWAY anti-HER-2/neu [4B5] Rabbit Monoclonal Primary Antibody assay or INFORM HER2 Dual ISH DNA Probe Cocktail assay).

A novel tumor metabolism-altering oral regimen that combines a tyrosine derivative (D,L-­alpha-metyrosine) with 3 repurposed agents (sirolimus, phenytoin, and methoxsalen) has demonstrated promising activity in patients with previously treated metastatic pancreatic cancer.

Sacituzumab govitecan, a novel antibody-drug conjugate directed against Trop-2, induced responses in nearly 33% of patients with heavily pretreated, relapsed or refrac­tory metastatic urothelial cancer.

Ovarian cancers with BRCA mutations are less immunogenic than other DNA re­pair–deficient tumors. Targeting the DNA damage response using PARP inhibitors may help to improve the modest responses of ovarian cancer seen with single-agent immune checkpoint inhibitors.

Moving combination immunotherapy into the neoadjuvant setting for patients with stage III melanoma induces a higher rate of pathologic response than adjuvant therapy, said Christian U. Blank, MD, PhD, Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, ­Amsterdam, at the 2019 ASCO-SITC Clinical Immuno-Oncology Symposium.

Darolutamide, an investigational androgen receptor inhibitor, significantly improved metastasis-free survival in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC) compared with placebo in a large phase 3 clinical trial.

First-line therapy with pembrolizumab (Keytruda) plus ­axitinib (Inlyta) significantly improved overall survival (OS), progression-free survival (PFS), and objective response rates compared with standard-of-care sunitinib (Sutent) in patients with clear-cell metastatic renal-cell carcinoma (RCC) in KEYNOTE-426.