Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Current and Future Trends

Càncer de mama metastàtic; Teràpies dirigides; TrastuzumabMetastatic breast cancer; Targeted therapies; TrastuzumabCáncer de mama metastásico; Terapias dirigidas; TrastuzumabApproximately 20% of breast cancers (BC) overexpress human epidermal growth factor receptor 2 (HER2). This subtype of BC is a clinically and biologically heterogeneous disease that was associated with an increased risk for the development of systemic and brain metastases and poor overall survival before anti-HER2 therapies were developed. The standard of care was dual blockade with trastuzumab and pertuzumab as first-line followed by TDM-1 as second-line. However, with the advent of new HER2-targeted monoclonal antibodies, tyrosine kinase inhibitors and antibody- drug conjugates, the clinical outcomes of patients with HER2-positive BC have changed dramatically in recent years, leading to a paradigm shift in the treatment of the disease. Notably, the development of new-generation ADCs has led to unprecedented results compared with T-DM1, currently establishing trastuzumab deruxtecan as a new standard of care in second-line. Despite the widespread availability of HER2-targeted therapies, patients with HER2-positive BC continue to face the challenges of disease progression, treatment resistance, and brain metastases. Response rate and overall life expectancy decrease with each additional line of treatment, and tumor heterogeneity remains an issue. In this review, we update the new-targeted therapeutic options for HER2-positive BC and highlight the future perspectives of treatment in this setting

Apalutamide for prostate cancer: multicentre and multidisciplinary real-world study of 227 patients

Apalutamide; Metastatic hormone-sensitive prostate cancer; Prostate cancerApalutamida; Cáncer de próstata metastásico sensible a hormonas; Cáncer de prostataApalutamida; Càncer de pròstata metastàtic sensible a les hormones; Càncer de pròstataObjective: To evaluate the efficacy and safety of apalutamide prostate cancer compared to the pivotal trials patients and to identify the first subsequent therapy in a real-world setting. Methods: The study is prospective and observational based on real-world evidence, performed by different medical disciplines and eight academics centres around Barcelona, Spain. It included all patients with metastatic hormone-sensitive prostate cancer (mHSPC) and high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide from June 2018 to December 2022. Results: Of 227 patients treated with apalutamide, 10% had ECOG-PS 2, and 41% were diagnosed with new-generation imaging. In the mHSPC group (209 patients), 75 years was the median age, 53% had synchronous metastases, and 22% were M1a. In the nmCRPC (18 patients), 82 years was the median age, and 81% ≤6 months had PSA doubling time. Patients achieved PSA90 in 92% of mHSPC and 50% of nmCRPC and PSA ≤0.2 in 71% of mHSPC and 39% of nmCRPC. Treatment-related adverse events occurred in 40.1% of mHSPC and 44.4% of nmCRPC. After discontinuation of apalutamide due to disease progression, 54.5% in mHSPC and 75% in nmCRPC started chemotherapy, while after discontinuation because of adverse events, 73.3% in mHSPC and 100% in nmCRPC continued with other hormonal-therapies.This study did not receive funding. Julián Córdoba and Meritxell Pérez have received sponsorship from Janssen for medical congresses and symposiums. Alejo Rodriguez- Vida, Jesús Muñoz Rodriguez, Antonio Alcaraz and Antoni Vilaseca have received honoraria from Janssen for advisory board meetings, symposiums and travel ex-penses. The other authors declare no conflict of interest. Approval of the research protocol by an Institutional Reviewer Board: HCB/2019/0919

Update in collecting duct carcinoma: Current aspects of the clinical and molecular characterization of an orphan disease

Bellini carcinoma; Clear-cell carcinoma; Collecting ductCarcinoma de Bellini; Carcinoma de cèl·lules clares; Conducte col·lectorCarcinoma de Bellini; Carcinoma de células claras; Conducto colectorCollecting duct renal cell carcinoma (cdRCC), which until recently was thought to arise from the collecting ducts of Bellini in the renal medulla, is a rare and aggressive type of non-clear renal cell carcinoma (ncRCC), accounting for 1% of all renal tumors and with nearly 50% of patients being diagnosed with Stage IV disease. The median overall survival in this setting is less than 12 months. Several regimens of chemotherapies had been used based on morphologic and cytogenetic similarities with urothelial cell carcinoma described previously, although the prognosis still remains poor. The use of targeted therapies also did not result in favorable outcomes. Recent works using NGS have highlighted genomic alterations in SETD2, CDKN2A, SMARCB1, and NF2. Moreover, transcriptomic studies have confirmed the differences between urothelial carcinoma and cdRCC, the possible true origin of this disease in the distal convoluted tubule (DCT), differentiating from other RCC (e.g., clear cell and papillary) that derive from the proximal convoluted tubule (PCT), and enrichment in immune cells that may harbor insights in novel treatment strategies with immunotherapy and target agents. In this review, we update the current aspects of the clinical, molecular characterization, and new targeted therapeutic options for Collecting duct carcinoma and highlight the future perspectives of treatment in this setting

Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Current and Future Trends

Approximately 20% of breast cancers (BC) overexpress human epidermal growth factor receptor 2 (HER2). This subtype of BC is a clinically and biologically heterogeneous disease that was associated with an increased risk for the development of systemic and brain metastases and poor overall survival before anti-HER2 therapies were developed. The standard of care was dual blockade with trastuzumab and pertuzumab as first-line followed by TDM-1 as second-line. However, with the advent of new HER2-targeted monoclonal antibodies, tyrosine kinase inhibitors and antibody- drug conjugates, the clinical outcomes of patients with HER2-positive BC have changed dramatically in recent years, leading to a paradigm shift in the treatment of the disease. Notably, the development of new-generation ADCs has led to unprecedented results compared with T-DM1, currently establishing trastuzumab deruxtecan as a new standard of care in second-line. Despite the widespread availability of HER2-targeted therapies, patients with HER2-positive BC continue to face the challenges of disease progression, treatment resistance, and brain metastases. Response rate and overall life expectancy decrease with each additional line of treatment, and tumor heterogeneity remains an issue. In this review, we update the new-targeted therapeutic options for HER2-positive BC and highlight the future perspectives of treatment in this setting

Apalutamide for prostate cancer: Multicentre and multidisciplinary real‐world study of 227 patients

Abstract Objective To evaluate the efficacy and safety of apalutamide prostate cancer compared to the pivotal trials patients and to identify the first subsequent therapy in a real‐world setting. Methods The study is prospective and observational based on real‐world evidence, performed by different medical disciplines and eight academics centres around Barcelona, Spain. It included all patients with metastatic hormone‐sensitive prostate cancer (mHSPC) and high‐risk non‐metastatic castration‐resistant prostate cancer (nmCRPC) treated with apalutamide from June 2018 to December 2022. Results Of 227 patients treated with apalutamide, 10% had ECOG‐PS 2, and 41% were diagnosed with new‐generation imaging. In the mHSPC group (209 patients), 75 years was the median age, 53% had synchronous metastases, and 22% were M1a. In the nmCRPC (18 patients), 82 years was the median age, and 81% ≤6 months had PSA doubling time. Patients achieved PSA90 in 92% of mHSPC and 50% of nmCRPC and PSA ≤0.2 in 71% of mHSPC and 39% of nmCRPC. Treatment‐related adverse events occurred in 40.1% of mHSPC and 44.4% of nmCRPC. After discontinuation of apalutamide due to disease progression, 54.5% in mHSPC and 75% in nmCRPC started chemotherapy, while after discontinuation because of adverse events, 73.3% in mHSPC and 100% in nmCRPC continued with other hormonal‐therapies. Conclusions The efficacy and safety of apalutamide were similar to that described in the pivotal trials, despite including an older and more comorbid population. Usually, subsequent therapies after apalutamide differed depending on the reason for discontinuation: by disease progression started chemotherapy and by adverse events hormonal sequencing