Perioperative Tailored Treatments for Gastric Cancer: Times Are Changing.

Resectable gastric or gastroesophageal (G/GEJ) cancer is a heterogeneous disease with no defined molecularly based treatment strategy. Unfortunately, nearly half of patients experience disease recurrence despite standard treatments (neoadjuvant and/or adjuvant chemotherapy/chemoradiotherapy and surgery). In this review, we summarize the evidence of potential tailored approaches in perioperative treatment of G/GEJ cancer, with a special focus on patients with human epidermal growth factor receptor-2(HER2)-positive and microsatellite instability-high (MSI-H) tumors. In patients with resectable MSI-H G/GEJ adenocarcinoma, the ongoing INFINITY trial introduces the concept of non-operative management for patients with complete clinical-pathological-molecular response, and this could be a novel and potential practice changing strategy. Other pathways involving vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), claudin18 isoform 2 (CLDN18.2), and DNA damage repair proteins are also described, with limited evidence until now. Although tailored therapy appears to be a promising strategy for resectable G/GEJ cancer, there are several methodological issues to address: inadequate sample size for pivotal trials, underestimation of subgroup effects, and choice of primary endpoint (tumor-centered vs. patient-centered endpoints). A better optimization of G/GEJ cancer treatment allows maximizing patient outcomes. In the perioperative phase, although caution is mandatory, times are changing and tailored strategies could introduce new treatment concepts. Overall, MSI-H G/GEJ cancer patients possess the characteristics to be the subgroup that could receive the most benefit from a tailored approach.

Immune checkpoint inhibitor-induced neurologic toxicity: a case report and literature review.

Immune checkpoint inhibitors (ICIs) are approved for the treatment of head and neck carcinoma. They have significantly improved survival in these patients but may cause immune-related adverse events (irAEs), some of which may be serious. The report presents a rare case of a neurologic adverse event associated with programmed death-1 inhibitor monotherapy. Neurologic irAEs (NirAEs) can occur in various and atypical forms, be potentially disabling and occur at various times during and after treatment. Prompt identification and drug withdrawal are essential to improve outcomes. A high dose of systemic corticosteroid has been recommended for the management of NirAEs, although optimal immunomodulatory treatment is still debated.

Current recommendations for head and neck squamous cell carcinoma treatments have been significantly modified after the introduction of immunotherapy. Indeed, immune checkpoint inhibitors (ICIs) are now recommended in localized and metastatic disease. Programmed death ligand-1 (PD-L1)-positive tumors can be treated with immunotherapy in the first and second lines regardless of PD-L1 expression. By increasing immune system activity, ICIs can have adverse effects. In most cases, these can be treated with the interruption of treatment and/or supportive therapy, which can include the administration of immunosuppressants. This report describes a case of suspected a neurologic adverse event characterized by trouble with balance and double vision in a person with head and neck cancer treated with nivolumab. This was adverse event was by pausing therapy and low-dose steroid treatment, leading to complete reduction of symptoms. Unfortunately, the laboratory and instrumental investigations could not determine an exact diagnosis or the area of neurological damage.

Lenvatinib: established and promising drug for the treatment of advanced hepatocellular carcinoma.

INTRODUCTION: : The evolving therapeutic landscape of advanced hepatocellular carcinoma (HCC) includes the increasing implementation of target-therapy and immunotherapy. Lenvatinib, a multi-target tyrosine kinase inhibitor (TKI), is an emerging first-line therapy for hepatocellular carcinoma. Its approval has changed the scenario of first-line therapies for advanced HCC, where just sorafenib proved clinical efficacy for over a decade. AREAS COVERED: : The current evidence on the role of lenvatinib for patients with advanced HCC is reviewed in this article. Particularly, therapeutic mechanisms and clinical efficacy of lenvatinib are summarized and the management of adverse events is discussed. In addition, future perspectives on the emerging role of combine therapy for HCC are highlighted. EXPERT OPINION: In the first line, lenvatinib was found to be non-inferior to sorafenib for overall survival, with significantly better progression-free survival and objective response rate. Immune checkpoint inhibitors (ICIs) are now part of HCC treatment, and recently the combination of atezolizumab plus bevacizumab has become the recommended standard of care first-line therapy for selected patients. The antitumor and immunomodulatory activities that lenvatinib shows in preclinical studies, and the positive outcomes achieved using a combination of lenvatinib plus ICIs, open new perspectives for advanced HCC treatment.

Immune Checkpoint Inhibitors in Urothelial Bladder Cancer: State of the Art and Future Perspectives.

Bladder cancer (BC) is the most common malignancy of the genitourinary tract, with high morbidity and mortality rates. Until recently, the treatment of locally advanced or metastatic urothelial BC was based on the use of chemotherapy alone. Since 2016, five immune checkpoint inhibitors (ICIs) have been approved by the Food and Drug Administration (FDA) in different settings, i.e., first-line, maintenance and second-line treatment, while several trials are still ongoing in the perioperative context. Lately, pembrolizumab, a programmed death-1 (PD-1) inhibitor, has been approved for Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), using immunotherapy at an early stage of the disease. This review investigates the current state and future perspectives of immunotherapy in BC, focusing on the rationale and results of combining immunotherapy with other therapeutic strategies.