Background/Objectives: Lung cancer is the leading cause of cancer-related deaths worldwide. Non-Small-Cell Lung Cancer (NSCLC) accounts for 80–90% of all lung cancers. Antibody-Drug Conjugates (ADCs) represent an expanding targeted therapy option for the treatment of NSCLC. The aim is to perform a systematic literature review to evaluate the efficacy and safety profiles of ADCs currently undergoing clinical trials for the treatment of NSCLC. Methods: The study adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Literature searches were conducted in PubMed, ClinicalTrial.gov and Web of Science databases, covering the period from 2014 to 2024. Only randomized and non-randomized phase II-IV clinical trials focusing on ADC-based therapies for adult patients affected by NSCLC were selected. The Revised Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2.0) and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) were used to evaluate the overall risk of bias in the included randomized and non-randomized studies, respectively. While GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology was used to assess the certainty of the evidence. Efficacy endpoints were categorized based on primary outcomes while safety was assessed through the frequency and severity of Treatment-Emergent Adverse Events (TEAEs), and a qualitative summary of the findings was conducted. Results: A total of seven studies, including three randomized, three non-randomized, and one without specific allocation, were included, comprising 1287 patients, with 693 (54%) men, and an average age of 63 years old. Two studies were deemed to have a low risk of bias, while six had a moderate risk or some concerns. Five ADCs were evaluated: trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), telisotuzumab vedotin, patritumab deruxtecan, and datopotamab deruxtecan (Dato-DXd). T-DXd demonstrated superior efficacy in HER2-overexpressing and HER2-mutant NSCLC, with an ORR of 52.9% and 49.0%, respectively. However, HER2-mutant patients exhibited a longer median DOR (16.8 vs. 6.2 months) but a higher incidence of grade ≥ 3 TEAEs (38.6% vs. 22%). T-DM1 showed modest efficacy, with an ORR of 20% in HER2-overexpressing NSCLC and 6.7% in HER2-mutant patients. Dato-DXd demonstrated improved ORR (26.4% vs. 12.8%) and PFS (4.4 vs. 3.7 months) compared to docetaxel. Patritumab deruxtecan achieved an ORR of 39% in EGFR-mutant NSCLC, while telisotuzumab vedotin exhibited limited activity in c-MET-positive NSCLC (ORR 9%, median DOR 7.5 months). Frequency and severity of TEAEs varied across ADCs, with ILD being a major concern, highlighting the need for strict patient monitoring and early intervention to mitigate severe adverse events. Conclusions: ADCs represent a promising advancement in NSCLC treatment, offering targeted therapeutic options beyond conventional chemotherapy and immunotherapy. T-DXd has emerged as the most effective ADC for HER2-mutant NSCLC with manageable safety profile, whereas Dato-DXd provides a viable alternative for TROP2-expressing tumors. While ADCs offer significant clinical benefits, careful patient selection and proactive management of adverse events remain crucial. Ongoing and future trials will further refine the role of ADCs in personalized NSCLC treatment, potentially expanding their tumor-agnostic use to broader patient populations.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, life-threatening lung disease with a global incidence of 0.09–1.30 per 10,000 individuals. Pirfenidone and nintedanib are the approved treatments for IPF. Objectives: This study evaluated the real-world safety and tolerability profiles of pirfenidone and nintedanib in IPF patients treated at the Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS ISMETT). A comparative analysis was conducted based on the number, types, and severity of adverse drug reactions (ADRs) and to identify potential predictors of treatment discontinuation or ADR onset based on patient characteristics. Design: A retrospective observational study was conducted on 531 IPF patients treated at IRCCS ISMETT with either pirfenidone or nintedanib. Methods: Eligible patients were selected based on the logged monthly dispensations provided by the pharmacy service for both therapies. Covariates were extracted from electronic medical records (age, sex, body mass index, smoking history, comorbidities, forced vital capacity (FVC) %, diffusing capacity of the lung for carbon monoxide (DLCO) %, 6-minute walk test (6-MWT), polytherapy, oxygen therapy, drug switch, etc.). ADRs were categorized by severity and follow-up status, and further classified according to the Medical Dictionary for Regulatory Activities, specifying the Preferred Terms and the related System Organ Classes. Chi-square or Fisher’s exact test was used for categorical variables, and univariate and multiple logistic regression identified potential risk factors for ADR onset. Backward Stepwise logistic regression (BSLR) was used to determine independent variables associated with ADR occurrence. Results: The nintedanib group had more frequent ADRs related to gastrointestinal and hepatobiliary disorders, with nausea, diarrhea, anorexia, and weight loss as the most common. The pirfenidone group had more ADRs related to skin, nervous system, and vascular disorders, such as rash, nausea, dizziness, and blood pressure imbalances. Significant baseline differences between groups included age, smoking status, FVC (%), DLCO (%), and 6-MWT, with the nintedanib cohort showing worse baseline characteristics. A total of 450 ADRs were reported: 59.6% for nintedanib and 40.4% for pirfenidone. Independent variables that significantly increased the likelihood of experiencing ADR were drug change, treatment type, gender, and age. Conclusion: Identifying ADR predictors is essential for personalizing treatment strategies. Both pirfenidone and nintedanib are crucial in managing IPF, highlighting the need for further research to optimize personalized therapies and patient outcomes.

Gender‐Affirming Hormone Therapy (GAHT) is a cornerstone of transgender care which induces profound physiological changes and significantly impacts pharmacokinetics and drug dosing strategies. This narrative review examines the clinical implications of GAHT, with a particular focus on renal function parameters, biomarkers, and challenges in the oncological setting. Evidence shows that GAHT considerably alters body composition, muscle mass and serum creatinine levels, resulting in fluctuations of standard calculations of creatinine clearance (CrCl) and estimated glomerular filtration rate (eGFR). Unfortunately, standardized dosing formulas remain unvalidated in transgender populations, although gender identity should guide renal function estimates and advocate for cautious interpretation and case‐by‐case assessment. Recent studies underscore the relevance of emerging biomarkers, such as cystatin C, as possible solutions for assessing renal function in transgender patients, since they are less influenced by body mass. Moreover, direct effects of exogenous hormones on renal physiology have also been highlighted, stressing the importance of thorough evaluation of all these factors, in order to ensure the accuracy of dosing algorithms based on gender‐affirming hormones. This issue becomes especially important in oncology, considering that improper use of antineoplastic agents may result in under or overdosing, especially for renally excreted or narrow therapeutic index drugs. Overall, this review aims to represent a resounding prompt to a multidisciplinary team of clinicians, pharmacists and pharmacologists that should play a crucial role in implementing safe, evidence‐based, and respectful individualized care pathways, particularly in complex clinical scenarios such as oncology.

Background: Cholangiocarcinoma (CCA) is a cancer with a low survival rate. New drugs targeting molecular alterations, oncogenic mutations, and gene fusions are being tested as second-line treatments. Objectives: This systematic review aims to summarize the results obtained with three new targeted therapies—pemigatinib, futibatinib, and ivosidenib—for the treatment of CCA, evaluating their safety and tolerability profiles in patients, compared to current standard therapies. Data sources and methods: A systematic literature search was performed with a cutoff date of July 24, 2023, in MEDLINE, Embase, and the Cochrane Library. The authors also conducted an advanced search in the ClinicalTrials.gov database, evaluated conference abstracts, article bibliographies, and drug monographs. Studies involving the treatment of patients with pemigatinib, futibatinib, and ivosidenib were considered. The selected studies had to report adverse events (AEs) that occurred during treatment with these therapies. Results: The most common AEs observed with pemigatinib, futibatinib, and ivosidenib were alopecia, diarrhea, fatigue, and dysgeusia. In addition, hyperphosphatemia, hypophosphatemia, and ocular disorders were observed with fibroblast growth factor receptor (FGFR) inhibitors, while the isocitrate dehydrogenase 1 (IDH1) inhibitor was associated with dose-dependent prolongation of the corrected QT interval (QTc). These AEs were effectively managed through dose adjustments. Conclusion: FGFR2 and IDH1 inhibitors have good tolerability in the population examined. All AEs were optimally managed with dose modulation. Future studies should focus on identifying the most effective dosages to further enhance treatment safety.

The SARS-CoV-2 infection has been associated with important mortality, particularly in immunocompromised patients, including solid organ transplant (SOT) recipients. Remdesivir (RDV) is an antiviral drug that has proven to be effective in reducing the replication of the virus in host cells, by which it may reduce the progression of symptoms and, consequently, the length of hospital stay and mortality. Randomized controlled trials have evaluated its use in the general population but never in SOT recipients. For the first time in this review, the safety and efficacy of RDV is evaluated in this specific population. The literature research was conducted using PubMed/MEDLINE and Scopus databases from 1 January 2020 to 24 November 2023, and 23 studies were analyzed. Although no clinical studies specifically evaluating this population have been conducted yet, RDV is likely safe for SOT patients when compared to the general population, so prescribers should consider utilizing RDV in SOT patients who are at high risk for progression to severe COVID-19. Future research will allow for the confirmation of the observed results and the acquisition of broader and clearer data regarding the safety and efficacy of the drug in this specific setting.