Simple Summary Brain metastases (BM) may affect a large portion of metastatic HER2-positive BC patients. Dual human epidermal growth factor receptor 2 (HER2) blockade with Pertuzumab and Trastuzumab (PT) in conjunction with chemotherapy represents the first line therapy of metastatic HER2- positive breast cancer (BC) and shows to prolong time to BM development as the first site of disease progression. When limited brain disease occurs with stable extracranial disease, current guidelines suggest to continue systemic therapies and add local brain treatment. However not data are available on the association between PT and stereotactic brain radiotherapy (SRT). This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and PT in patients with breast cancer BM. Abstract (1) Background: This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and pertuzumab–trastuzumab (PT) in patients with breast cancer brain metastases (BCBM). (2) Methods: Patients with HER2+ BCBM who received FSRT from 2015 to 2019 were identified. Patients were included if they were treated with fSRT within 21 days of receiving PT. All lesions were treated with LINAC-based fSRT to a total dose of 27 Gy delivered in three consecutive fractions. All patients received concurrent PT. Patients were evaluated 4–6 weeks after SRS and subsequently every 2–3 months with MRI re-imaging (3) Results: A total of 49 patients with HER2+ brain metastases were identified. Of these patients, a total of 10 patients with 32 HER2+ BCBM were treated with concurrent SRT and PT and included in the analysis. No local progression was observed. Overall response rate was 68.7%. Only one patient developed asymptomatic radionecrosis. Median time to BM occurrence was 15.6 (range: 1–40.5 months). Distant intracranial failure occurred in 4/10 patients (40.0%). Overall BCBM median survival was 33.9 months (95%CI 24.1–43.6). Mean duration of PT treatment was 27.9 months (range: 10.1–53.7 months). (4) Conclusions: In our single institution experience, fSRT and PT showed to be a safe treatment for patients with BCBM with an adequate overall response rate.

/pdf/stereotactic-radiation-and-dual-human-epidermal-growth-740y7s6z.pdf

Stereotactic Radiation and Dual Human Epidermal Growth Factor Receptor 2 Blockade with Trastuzumab and Pertuzumab in the Treatment of Breast Cancer Brain Metastases: A Single Institution Series

Glioblastoma is the most common primary malignant tumor in the brain and has a dismal prognosis despite patients accepting standard therapies. Alternation of genes and deregulation of proteins, such as receptor tyrosine kinase, PI3K/Akt, PKC, Ras/Raf/MEK, histone deacetylases, poly (ADP-ribose) polymerase (PARP), CDK4/6, branched-chain amino acid transaminase 1 (BCAT1), and Isocitrate dehydrogenase (IDH), play pivotal roles in the pathogenesis and progression of glioma. Simultaneously, the abnormalities change the cellular biological behavior and microenvironment of tumor cells. The differences between tumor cells and normal tissue become the vulnerability of tumor, which can be taken advantage of using targeted therapies. Small molecule inhibitors, as an important part of modern treatment for cancers, have shown significant efficacy in hematologic cancers and some solid tumors. To date, in glioblastoma, there have been more than 200 clinical trials completed or ongoing in which trial designers used small molecules as monotherapy or combination regimens to correct the abnormalities. In this review, we summarize the dysfunctional molecular mechanisms and highlight the outcomes of relevant clinical trials associated with small-molecule targeted therapies. Based on the outcomes, the main findings were that small-molecule inhibitors did not bring more benefit to newly diagnosed glioblastoma, but the clinical studies involving progressive glioblastoma usually claimed “noninferiority” compared with historical results. However, as to the clinical inferiority trial, similar dosing regimens should be avoided in future clinical trials.

/pdf/small-molecule-inhibitors-in-adult-high-grade-glioma-from-1f5acvca.pdf

Small Molecule Inhibitors in Adult High-Grade Glioma: From the Past to the Future

Penoscrotal extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma in older male patients, and no effective nonsurgical treatment strategies are currently available. The aim o...

https://journals.sagepub.com/doi/pdf/10.1177/11795476211009251

Definitive Radiotherapy for Penoscrotal Extramammary Paget’s Disease: A Case Report with Long-Term Follow-Up:

Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with many anticancer therapies and can negatively impact patients' quality of life and potentially limit the effectiveness of chemotherapy. Currently, CINV can be prevented in most patients with guideline-recommended antiemetic regimens. However, clinicians do not always follow guidelines, and patients often face difficulties adhering to their prescribed treatments. Therefore, approaches to increase guideline adherence need to be implemented. NEPA is the first and only fixed combination antiemetic, composed of netupitant (oral)/fosnetupitant (intravenous) and palonosetron, which, together with dexamethasone, constitute a triple antiemetic combination recommended for the prevention of CINV for patients receiving highly emetogenic chemotherapy and for certain patients receiving moderately emetogenic chemotherapy. Thus, NEPA offers a convenient and straightforward antiemetic treatment that could improve adherence to guidelines. This review provides an overview of CINV, evaluates the accumulated evidence of NEPA's antiemetic activity and safety from clinical trials and real-world practice, and examines the preliminary evidence of antiemetic control with NEPA in daily clinical settings beyond those described in pivotal trials. Moreover, we review the utility of NEPA in controlling nausea and preserving patients’ quality of life during chemotherapy, two major concerns in managing patients with cancer.

https://doi.org/10.2174/1568009622666220513094352

Netupitant-palonosetron (NEPA) for Preventing Chemotherapy-induced Nausea and Vomiting: From Clinical Trials to Daily Practice

Simple Summary Patients with HER2-positive metastatic breast cancer develop brain metastases in up to 30% of cases. The aim of this systematic review and meta-analysis was to determine the effect of different systemic therapies in patients with HER2-positive metastatic breast cancer and brain metastases, acknowledging the heterogeneity and sometimes low quality of 51 included studies. Tucatinib (combined with trastuzumab and capecitabine) and trastuzumab-deruxtecan appear to constitute the most effective systemic therapy, while pyrotinib might be an option in Asian patients. Preferably, future research will comprise of randomized controlled trials, including patients with active and/or inactive brain metastases. Abstract Aim: Patients with HER2-positive (HER2+) metastatic breast cancer (mBC) develop brain metastases (BM) in up to 30% of cases. Treatment of patients with BM can consist of local treatment (surgery and/or radiotherapy) and/or systemic treatment. We undertook a systematic review and meta-analysis to determine the effect of different systemic therapies in patients with HER2+ mBC and BM. Methods: A systematic search was performed in the databases PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection and the Wiley/Cochrane Library. Eligible articles included prospective or retrospective studies reporting on the effect of systemic therapy on objective response rate (ORR) and/or median progression free survival (mPFS) in patients with HER2+ mBC and BM. The timeframe within the databases was from inception to 19 January 2022. Fixed-effects meta-analyses were used. Quality appraisal was performed using the ROBINS-I tool. Results: Fifty-one studies were included, involving 3118 patients. Most studies, which contained the largest patient numbers, but also often carried a moderate-serious risk of bias, investigated lapatinib and capecitabine (LC), trastuzumab-emtansine (T-DM1) or pyrotinib. The best quality data and/or highest ORR were described with tucatinib (combined with trastuzumab and capecitabine, TTC) and trastuzumab-deruxtecan (T-DXd). TTC demonstrated an ORR of 47.3% in patients with asymptomatic and/or active BM. T-DXd achieved a pooled ORR of 64% (95% CI 43–85%, I2 0%) in a heavily pretreated population with asymptomatic BM (3 studies, n = 96). Conclusions: Though our meta-analysis should be interpreted with caution due to the heterogeneity of included studies and a related serious risk of bias, this review provides a comprehensive overview of all currently available systemic treatment options. T-Dxd and TTC that appear to constitute the most effective systemic therapy in patients with HER2+ mBC and BM, while pyrotinib might be an option in Asian patients.

/pdf/systemic-therapy-for-patients-with-her2-positive-breast-1abm5nru.pdf

Systemic Therapy for Patients with HER2-Positive Breast Cancer and Brain Metastases: A Systematic Review and Meta-Analysis

Brain metastases (BMs) are frequently associated with HER2+ breast cancer (BC). Their management is based on a multi-modal strategy including both local treatment and systemic therapy. Despite therapeutic advance, BMs still have an adverse impact on survival and quality of life and the development of effective systemic therapy to prevent and treat BMs from HER2 + BC represents an unmet clinical need. Trastuzumab-based therapy has long been the mainstay of systemic therapy and over the last two decades other HER2-targeted agents including lapatinib, pertuzumab and trastuzumab emtansine, have been introduced in the clinical practice. More recently, novel agents such as neratinib, tucatinib and trastuzumab deruxtecan have been developed, with interesting activity against BMs. Further research is needed to better elucidate the best sequence of these agents and their combination with local treatment.

Current treatment options for HER2-positive breast cancer patients with brain metastases.

IntroductionChemotherapy-induced nausea and vomiting (CINV) may affect adherence to planned chemotherapy treatments and compromise patients’ quality of life during the therapy. NEPA is an oral fixe...

NEPA as antiemetic prophylaxis after failure of 5HT3-RA plus dexamethasone in patients receiving carboplatin and gemcitabine chemotherapy: A monocentric real-life experience:

Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma generally arising in the anogenital region Surgery is still considered the treatment of choice for patients with EMPD, while Radiotherapy is a common alternative for inoperable cases and it's necessary in case of lack of surgical radicality In this article, we described our experience and a review of the literature, with a particular focus on radiation-induced toxicity and on the feasibility of re-irradiation A 70-year-old patient with EPMD underwent adjuvant radiotherapy in 2015 After 28 months for recurrence another radiant treatment was performed No G3 (CTCAE v4) toxicity were recorded In the last follow-up visit at 18 months, no signs of relapse were reported A search strategy of the bibliographic database PubMed was performed The inclusion criteria for the articles were case report, clinical prospective, or retrospective studies with histological confirmation of EMPD of scrotum and penis; studies with patients undergoing RT; studies in the past 30 years In most of the 14 reported studies, RT was overall well tolerated The major observed toxicity was G3 skin toxicity in one study To our knowledge, there are no other cases of EPMD re-irradiation in literature Our patient showed an excellent response and tolerated very well the high doses of both the radiation treatments This suggests that the tolerance of skin to re-irradiation following a long period between the two treatments may be comparable to the normal constraints

Maria La Vecchia

Papers

Current treatment options for HER2-positive breast cancer patients with brain metastases.

NEPA as antiemetic prophylaxis after failure of 5HT3-RA plus dexamethasone in patients receiving carboplatin and gemcitabine chemotherapy: A monocentric real-life experience:

Paget's disease of scrotum and penis case report of a re-irradiation and review of the literature.