Genes Involved in Immune Reinduction May Constitute Biomarkers of Response for Metastatic Melanoma Patients Treated with Targeted Therapy.

Targeted therapy in metastatic melanoma often achieves a major tumour regression response and significant long-term survival via the release of antigens that reinduce immunocompetence. The biomarkers thus activated may guide the prediction of response, but this association and its mechanism have yet to be established. Blood samples were collected from nineteen consecutive patients with metastatic melanoma before, during, and after treatment with targeted therapy. Differential gene expression analysis was performed, which identified the genes involved in the treatment, both in the first evaluation of response and during progression. Although clinical characteristics of the patients were poorer than those obtained in pivotal studies, radiological responses were similar to those reported previously (objective response rate: 73.7%). In the first tumour assessment, the expression of some genes increased (CXCL-10, SERPING1, PDL1, and PDL2), while that of others decreased (ARG1, IL18R1, IL18RAP, IL1R1, ILR2, FLT3, SLC11A1, CD163, and S100A12). The analysis of gene expression in blood shows that some are activated and others inhibited by targeted therapy. This response pattern may provide biomarkers of the immune reinduction response, which could be used to study potential combination treatments. Nevertheless, further studies are needed to validate these results.

Toxicity of docetaxel, carboplatin, and trastuzumab combination as adjuvant or neo-adjuvant treatment for Her2 positive breast cancer patients and impact of colony-stimulating factor prophylaxis.

While the docetaxel, carboplatin, and trastuzumab (TCH) regimen is one of the standard treatments in Her2-positive breast cancer, however, acute toxicities, especially those related to the high rate of neutropenia are consistently reported. Primary: To compare the toxicity of TCH in current clinical practice vs the toxicity observed in the pivotal study, comparing the toxicity in patients that received primary prophylaxis (PP) with colony-stimulating factors vs those that did not receive PP. Secondary: To describe the demographic and clinical characteristics of the study sample, as well as the adverse effects and survival. The data regarding 95 patients were analyzed. Observed toxicity (hematological and extra-hematological) was greater compared to the pivotal study, with the exception of neuropathy and neutropenia. Toxicities "PP" vs "no PP": Extra-hematological grade 3-4 toxicities: Significant reduction was observed in the "PP" group vs the "no PP" group referred to fatigue, stomatitis, nausea, and vomiting. Hematological grade 3-4 toxicities: Lesser neutropenia, leukopenia, and febrile neutropenia were observed in the "PP" group. Complications associated to treatment: No grade 3-4 cardiac toxicity, leukemia or deaths were recorded. DFS and OS: After a mean follow-up of 22.9 months, only one bone metastatic relapse was detected (DFS: 98.9%; OS: 100%). The combination TCH is very active and effective as adjuvant and neo-adjuvant therapy in Her2-positive breast cancer, and is currently regarded as standard treatment. However, global toxicity as well as hematological toxicity is elevated. The incorporation of PP to TCH significantly reduces hematological toxicity and some of the global toxicity, thus favoring treatment implementation and lessening the clinical complications. We therefore recommend generalization of PP with colony-stimulating factors in patients receiving TCH.