Kent Shih, MD, of Tennessee Oncology, presents three patients cases that show how the use of gene-expression profile testing guides patient and practitioner decision-making when choosing the appropriate path of adjuvant treatment among individuals with melanoma.
Erika Hamilton, MD, Director, Breast Cancer Research at Sarah Cannon Research Institute, provides a look at “where we stand in 2025” in the field of oral selective estrogen receptor degraders (SERDs) for patients with estrogen receptor–positive, HER2-negative breast cancer. She discusses the first and only FDA-approved oral SERD, elacestrant, indicated for use after CDK4/6 inhibitor therapy in patients with ESR1 mutations; reviews agents still being tested in clinical trials, such as imlunestrant and camizestrant; and highlights the role of oral SERDs as both monotherapies and in novel combinations. As Dr. Hamilton explains, “there haven’t been novel endocrine backbones [for these patients] since fulvestrant.”
Jennifer Gile, MD, of Willamette Valley Cancer Institute, talks about the first positive phase III trials in the high-risk diffuse large B-cell lymphoma (DLBCL) space—POLARIX and frontMIND. POLARIX established the superiority of a modified regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) called pola-R-CHP, in which vincristine was replaced with polatuzumab vedotin, over standard R-CHOP; frontMIND showed that the addition of the CD19 monoclonal antibody tafasitamab plus the immunomodulatory drug lenalidomide to R-CHOP also improved outcomes over standard R-CHOP. Dr. Gile discusses current considerations when choosing between these regimens and how future research may lead to even more refined patient selection.
The phase III frontMIND trial demonstrated improved outcomes vs R-CHOP in high-risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), paralleling the POLARIX trial. Despite efficacy, tafasitamab/lenalidomide/R-CHOP has not achieved comparable guideline adoption. Uncertainty regarding overall survival benefit, limited follow-up, cross-trial comparisons, and implementation complexity may contribute to the underutilization of this regimen despite its manageable toxicity.
Raajit K. Rampal, MD, PhD, Director of the Center for Hematologic Malignancies and the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, reviews the four FDA-approved Janus kinase (JAK) inhibitors for patients with myelofibrosis, touching upon differences in their mechanisms of action and toxicity profiles. He also discusses clinical trials of add-on drugs to the currently approved JAK inhibitors, which may increase their efficacy and durability, as well as trials of novel JAK inhibitors and immunotherapies targeting CALR.
Allison Betof Warner, MD, PhD, reviews important clinical research in the treatment of advanced melanoma, including tumor-infiltrating lymphocyte (TIL) therapy, the role of this innovative treatment in advanced melanoma, and relevant data, peer-reviewed literature, and FDA approvals in 2024. She also provides a look ahead at what is on the horizon in 2025 with regard to care for patients with advanced melanoma.
