The therapeutic landscape for small cell lung cancer (SCLC) has remained stationary for decades, with chemotherapy representing the sole treatment strategy, with a modest survival benefit. The addition of immune checkpoint inhibitors (ICIs) to standard first-line chemotherapy for SCLC was a considerable milestone. However, despite high overall response rates, this strategy failed to deliver long-term benefits for most patients, who continue to face a poor prognosis. Over the last few years, a deeper knowledge of the molecular biology of SCLC and the impressive advancements in drug development, have led to the generation of novel classes of systemic therapies that promise to revolutionize the current therapeutic scenario. Among the various therapeutic approaches in development, T-cell Engagers (TCE) and antibody-drug conjugates (ADCs) stand out due to their unique structural characteristics and mechanisms of action. These therapies represent a paradigm shift from traditional monoclonal antibody (mAb) and chemotherapy regimens, allowing direct engagement of multiple targets associated with tumor progression. In this review, we provide an overview of current drug development in SCLC, specifically focusing on these new agents, summarizing available evidence, and tracking future directions.

Over the past decade, significant achievements in elucidating the molecular pathogenesis of non–small cell lung cancer (NSCLC) have catalyzed a paradigm shift from empiric therapies to precision oncology. In this context, HER2 alterations, including protein overexpression, gene amplification, and activating mutations, constitute distinct molecular subsets within NSCLC. In the past few years, targeted therapeutic modalities such as antibody–drug conjugates (ADCs), particularly trastuzumab deruxtecan (the first agent to be granted FDA approval for HER2-mutant NSCLC), alongside selective tyrosine kinase inhibitors (TKIs), including zongertinib and sevabertinib, have demonstrated robust systemic efficacy and notable intracranial penetration. This comprehensive review delineates the molecular landscape and clinical phenotypes of HER2-altered NSCLC, synthesizes interim and mature data from ongoing clinical trials evaluating anti-HER2 therapies, and critically examines efficacy and safety results from different classes of targeted agents. Further research is crucial to uncover potential mechanisms of resistance in NSCLC with HER2 mutations and define sequencing or combinatorial strategies pertinent to optimizing individualized patient management.

Background: Olaparib and niraparib are poly (ADP-ribose) polymerase inhibitors (PARPi) used primarily for the treatment of ovarian cancer. While both drugs have demonstrated efficacy in clinical trials, their safety profiles, particularly in real-world clinical settings, remain to be fully elucidated. Objectives: This study aimed to (i) characterize the adverse drug reactions (ADRs) associated with olaparib and niraparib as reported in the EudraVigilance database, (ii) compare the frequency of the ADRs occurring during treatment with the two drugs, and (iii) compare post-marketing safety data with those from clinical trials. Methods: A retrospective analysis was performed using data from the EudraVigilance database (2017–2024), focusing on individual case safety reports (ICSRs) related to olaparib and niraparib. Descriptive statistics and disproportionality analysis were performed to compare the frequency and severity of reported ADRs. Results: Both olaparib and niraparib had common ADRs including nausea, vomiting, anemia, thrombocytopenia, and fatigue. However, olaparib was associated with a higher risk of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and interstitial lung disease, while niraparib had a higher incidence of gastrointestinal events and thrombocytopenia. Our analysis demonstrates that some specific ADRs, including peripheral neuropathy with niraparib, were reported at higher frequencies compared to clinical trials. The incidence of serious ADRs, including hospitalizations and life-threatening events, was higher with niraparib than with olaparib. Conclusions: This study highlights significant differences in the safety profiles of olaparib and niraparib, with implications for clinical decision-making. Continuous monitoring and personalized management of ADRs are essential to optimize patient outcomes.