Articles related to TARGETED THERAPIES

Per guidelines, cancers with HER2 expression with a score of 3+ was considered HER2-positive. Cancers with scores of 0 and 1+, or those with an IHC score of 2+ and a negative ISH result, have been characterized as HER2-negative. These guideline-directed binary distinctions — HER2-positive vs HER2-negative — have until now guided physicians’ treatment decisions. New research suggests that patients with HER2-2+, ISH-negative breast cancer present a clinical picture closer to that of patients with HER2-positive breast cancer.

In the study,155 FDA-approved drugs with 136 potentially targetable genes were identified.One-hundred forty-six (94%) of the drugs showed no or low genetically predicted drug response. Although ATC-carrying BRAF mutations can benefit from BRAF inhibitors and this effect might be enhanced by a combined strategy including PIK3CA inhibitors in some of the patients, alterations in BRAFWT ATC are not directly targeted by currently FDA-approved options.

This one-credit activity features an expert panel providing their perspectives on the latest trends and emerging research regarding biomarker testing and evidence-based biomarker-guided targeted therapy for patients with NSCLC with ROS1 and ALK rearrangements.

Targeted therapy gene mutations may: (a) encode a protein that can be targeted in a manner distinct from the WT protein; (b) cause abnormal activation of a protein that is druggable but for which mutant-specific targeting has not been achieved; or (c) create novel molecular dependencies that are druggable. This article describe key examples of genetic drivers and associated modes of druggability, considers the clinical and research challenges in the field, and discusses new approaches to maximizing therapeutic benefit of targeted therapies.

The phase 3 KEYNOTE-048 trial compares pembrolizumab with or without concurrent chemotherapy to cetuximab-chemotherapy in patients with recurrent or metastatic head and neck SCC. Patients were evaluated in subgroups based on PD-L1 expression. In median survival, pembrolizumab + chemotherapy outperformed cetuximab + chemotherapy in all patient subgroups regardless of PD-L1 expression. In the PD-L1 CPS 1-19 subgroup, pembrolizumab alone slightly outperformed cetuximab + chemotherapy. In the PD-L1 CPS < 1 subgroup median survival was significantly lower with pembrolizumab alone.

Mirvetuximab soravtansine is an antibody-drug conjugate that consists of an FRα-binding antibody, cleavable linker, and maytansinoid DM4, which is a potent tubulin-targeting agent. It was tested in a single-arm phase 3 trial that included 106 patients with platinum-resistant, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancers with high FRα expression. The investigator-assessed ORR was nearly triple the benchmark set in prior studies of less heavily pretreated platinum-resistant ovarian cancer populations. The ORR was similar regardless of the number of prior lines of therapy or prior PARP inhibitor exposure. The rapid and durable response seen with mirvetuximab in patients with FRα-positive, platinum-resistant ovarian cancer may position it to become a practice-changing, biomarker-driven standard of care treatment option.