Clinical Significance of Molecular Subtypes in Western Advanced Gastric Cancer: A Real-World Multicenter Experience.

In recent years, the molecular subtyping of gastric cancer has led to the identification of novel clinically relevant biomarkers as well as promising therapeutic targets. In parallel, the advent of checkpoint inhibitors has expanded treatment options beyond conventional chemotherapy. Compelling evidence has shown unprecedented efficacy results for anti-PD1-based therapies in the molecular subgroups of dMMR/MSI-h, EBV+ and PD-L1 CPS+ patients, to the point that these are granted approval for gastric cancer adenocarcinoma (AGC) in several countries. Despite this, cytotoxic chemotherapy remains the only treatment choice for the considerable proportion of biomarkers-negative patients. In this context, little is known about the association between subtypes-defining biomarkers (HER2, MMR/MSI, PD-L1, and EBV) and the efficacy of standard chemotherapy in non-Asian AGC. Here, we aimed to investigate the prevalence, the clinic-pathologic features, and the impact on treatment outcome of clinical molecular subtypes in a new-diagnosed Western cohort of AGC.

Impact of BMI on Survival Outcomes of Immunotherapy in Solid Tumors: A Systematic Review.

Growing research has focused on obesity as a prognostic factor during therapy with immune-checkpoint inhibitors (ICIs). The role of body-mass index (BMI) in predicting response and toxicity to ICIs is not clear, as studies have shown inconsistent results and significant interpretation biases. We performed a systematic review to evaluate the relationship between BMI and survival outcomes during ICIs, with a side focus on the incidence of immune-related adverse events (irAEs). A total of 17 studies were included in this systematic review. Altogether, the current evidence does not support a clearly positive association of BMI with survival outcomes. Regarding toxicities, available studies confirm a superimposable rate of irAEs among obese and normal weight patients. Intrinsic limitations of the analyzed studies include the retrospective nature, the heterogeneity of patients' cohorts, and differences in BMI categorization for obese patients across different studies. These factors might explain the heterogeneity of available results, and the subsequent absence of a well-established role of baseline BMI on the efficacy of ICIs among cancer patients. Further prospective studies are needed, in order to clarify the role of obesity in cancer patients treated with immunotherapy.

Oxaliplatin-Related Hypersensitivity Reactions: A Single Institution Series and Literature Review.

Oxaliplatin-based chemotherapy is extensively used for the treatment of gastrointestinal tumors and other malignancies. Oxaliplatin-related hypersensitivity reactions (HSRs) are common during antitumor treatment. Several studies have been conducted to identify predictive risk factors for oxaliplatin-related HSRs, but findings remain controversial. No definitive approach has been identified to reduce the risk of developing HSRs. The aim of this article is to provide an overview of oxaliplatin-related HSRs, and to report our institution's experience. With our work, we reviewed available data from the literature and described our case series. A total of 153 patients were treated with oxaliplatin and 17 developed an HSR. On the whole, 70.6% of reactions were Grade 3, mostly with respiratory and cutaneous symptoms. Steroids and antihistamines were administered to reduce hypersensitivity symptoms and prevent further reactions. A stronger premedication and prolonged time of infusion resulted in milder reactions or absence of subsequent reactions. We did not find any clear predictive factor for the development of HSRs. Although it is not possible to cancel the risk of oxaliplatin-based HSRs, strategies to reduce the risk of occurrence could be stronger premedication and prolonged time of infusion.

Nivolumab plus ipilimumab for the first-line treatment of metastatic NSCLC.

INTRODUCTION: In the last decade, immune checkpoint inhibitors have revolutionized the treatment of several malignancies including non-small cell lung cancer (NSCLC). The inhibition of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed death receptor 1 (PD-1) pathways leads to an activation of the immune response against tumor cells. Thanks to a synergistic effect, the combination of the checkpoint inhibitors nivolumab and ipilimumab has the potential to improve outcomes of NSCLC patients. AREAS COVERED: We provide an overview of clinical trials evaluating the combination of nivolumab and ipilimumab in the first-line treatment of advanced NSCLC patients. EXPERT OPINION: The combination of nivolumab and ipilimumab, alone or with a few cycles of chemotherapy, was demonstrated to be a valid option for first-line treatment of metastatic NSCLC patients without EGFR mutation and ALK rearrangement. However, a better understanding of patients who can benefit from this approach is required.