Clinical Impact of CDK4/6 Inhibitors in De Novo or PR- or Very Elderly Post-Menopausal ER+/HER2- Advanced Breast Cancers.

The CDK4/6 inhibitors significantly increase progression-free survival (PFS) in ER+/HER2- advanced breast cancer patients. In clinical trials, overall survival (OS) improvement has been demonstrated for ribociclib and abemaciclib but not for palbociclib. We undertook a real-world evaluation of PFS and OS in 227 post-menopausal patients who received first-line CDK4/6 inhibitors. There is no significant difference in median PFS (27.5 months vs. 25.7 months, p = 0.3) or median OS (49.5 months vs. 50.2 months, p = 0.67) in patients who received either palbociclib or ribociclib, respectively. De novo disease is significantly associated with prolonged median PFS and median OS compared with recurrence disease (47.1 months vs. 20.3 months (p = 0.0002) and 77.4 months vs. 37.3 months (p = 0.0003), respectively). PR- tumours have significantly reduced median PFS and OS compared with PR+ disease (19.2 months vs. 38 months (p = 0.003) and 34.3 months vs. 62.6 months (p = 0.02), respectively). In the very elderly (>80 years), median PFS and OS are significantly shorter compared with patients who are 65 years or below (14.5 months vs. 30.2 months (p = 0.01), and 77.4 months vs. 29.6 months (p = 0.009), respectively) in the palbociclib group. Our data suggest that the benefit in the very elderly is limited, and PR+/de novo disease obtains the maximum survival benefit.

CAR T-Cell Therapy for Cancer: Latest Updates and Challenges, with a Focus on B-Lymphoid Malignancies and Selected Solid Tumours.

Although exponential progress in treating advanced malignancy has been made in the modern era with immune checkpoint blockade, survival outcomes remain suboptimal. Cellular immunotherapy, such as chimeric antigen receptor T cells, has the potential to improve this. CAR T cells combine the antigen specificity of a monoclonal antibody with the cytotoxic 'power' of T-lymphocytes through expression of a transgene encoding the scFv domain, CD3 activation molecule, and co-stimulatory domains. Although, very rarely, fatal cytokine-release syndrome may occur, CAR T-cell therapy gives patients with refractory CD19-positive B-lymphoid malignancies an important further therapeutic option. However, low-level expression of epithelial tumour-associated-antigens on non-malignant cells makes the application of CAR T-cell technology to common solid cancers challenging, as does the potentially limited ability of CAR T cells to traffic outside the blood/lymphoid microenvironment into metastatic lesions. Despite this, in advanced neuroblastoma refractory to standard therapy, 60% long-term overall survival and an objective response in 63% was achieved with anti GD2-specific CAR T cells.

An Unusual Presentation of Deep Vein Thrombosis.

May-Thurner syndrome (MTS) usually presents as acute or chronic deep vein thrombosis (DVT) in patients. A 49-year-old woman presented with left lower limb DVT, which was followed by a diagnosis of MTS on a background of polycystic ovary syndrome (PCOS) and hypothyroidism. MTS is more common among women in the second to fourth decades of life. An endovascular approach is the preferred first-line treatment for MTS. LEARNING POINTS: This case highlights the importance of serial ultrasound Doppler scans in cases where the probability of deep vein thrombosis (DVT) is high as a negative initial Doppler scan does not exclude DVT.May-Thurner syndrome (MTS) should be suspected especially in younger patients in whom no cause for DVT has been found.Missing a diagnosis of MTS could result in life-threatening conditions such as pulmonary embolism and post-thrombotic syndrome.