Background: Small cell lung cancer (SCLC) remains a highly aggressive malignancy with a poor prognosis. Despite multimodal standard therapies, most patients relapse within months, and second-line treatment options such as topotecan offer only limited benefit. Novel therapeutic strategies are therefore urgently needed. Methods: This narrative review is based on a selective literature search conducted via PubMed and ClinicalTrials.gov (last updated June 2025). Results: Emerging treatment strategies include bispecific T-cell engagers (e.g., tarlatamab), antibody-drug conjugates (ADCs) such as sacituzumab govitecan, DS-7300, and ZL-1310, as well as targeted therapies. Among these, tarlatamab has demonstrated improved survival outcomes with an acceptable safety profile and is poised to become the new second-line standard. In contrast, ADCs and targeted agents have shown only modest efficacy and have yet to deliver meaningful survival benefits, often accompanied by increased toxicity. Additionally, the identification of molecular subtypes of SCLC has revealed subtype-specific differences in treatment response. However, clinical translation is challenged by intratumoral heterogeneity, plasticity, and the lack of standardized diagnostic assays. Conclusions: While tarlatamab represents a major therapeutic advancement, other agents remain in early clinical development and require validation in large, randomized trials. The clinical implementation of molecular subtyping remains limited, though it holds promise for future personalized treatment approaches. Despite recent progress, SCLC continues to pose substantial therapeutic challenges, emphasizing the need for improved treatment strategies and validated predictive biomarkers.

Background: Two-dose COVID-19 vaccination often results in poor humoral response rates in patients with hematologic malignancies (HMs); yet responses to COVID-19 booster vaccines and the risk of COVID-19 infection post-booster are mostly uncertain. Methods: We included 200 outpatients with HMs and predominantly lymphoid neoplasms (96%, 191/200) in our academic center and reported on the humoral responses, which were assessed by measurement of anti-spike IgG antibodies in peripheral blood as early as 14 days after mRNA-based prime-boost vaccination, as well as factors hampering booster efficacy. Previous basic (double) immunization was applied according to the local recommendations with mRNA- and/or vector-based vaccines. We also report on post-booster COVID-19 breakthrough infections that emerged in the Omicron era and the prophylaxis strategies that were applied to poor and non-responders to booster vaccines. Results: A total of 55% (110/200) of the patients achieved seroconversion (i.e., anti-spike protein IgG antibody titer > 100 AU/mL assessed in median 48 days after prime-boost vaccination) after prime-boost vaccination. Multivariable analyses revealed age, lymphocytopenia, ongoing treatment and prior anti-CD20 B-cell depletion to be independent predictors for booster failure. With each month between anti-CD20-mediated B-cell depletion and booster vaccination, the probability of seroconversion increased by approximately 4% (p < 0.001) and serum–antibody titer (S-AbT) levels increased by 90 AU/mL (p = 0.011). Notably, obinutuzumab treatment was associated with an 85% lower probability for seroconversion after prime-boost vaccination compared to rituximab (p = 0.002). Of poor or non-responders to prime-boost vaccination, 41% (47/114) underwent a second booster and 73% (83/114) underwent passive immunization. COVID-19 breakthrough infections were observed in 15% (29/200) of patients after prime-boost vaccination with predominantly mild courses (93%). Next to seroconversion, passive immunization was associated with a significantly lower risk of COVID-19 breakthrough infections after booster, even in vaccine non-responders (all p < 0.05). In a small proportion of analyzed patients with myeloid neoplasms (9/200), the seroconversion rate was higher compared to those with lymphoid ones (78% vs. 54%, accordingly), while the incidence rate of COVID-19 breakthrough infections was similar (22% vs. 14%, respectively). Following the low frequency of myeloid neoplasms in this study, the results may not be automatically applied to a larger cohort. Conclusions: Patients with HMs are at a high risk of COVID-19 booster vaccine failure; yet COVID-19 breakthrough infections after prime-boost vaccination are predominantly mild. Booster failure can likely be overcome by passive immunization, thereby providing immune protection against COVID-19 and attenuating the severity of COVID-19 courses. Further sophistication of clinical algorithms for preventing post-vaccination COVID-19 breakthrough infections is urgently needed.

COVID-19 vaccines have become an integral element in the protection of cancer patients against SARS-CoV-2. To date, there are no direct comparisons of the course of COVID-19 infection in cancer patients between the pre- and post-vaccine era. We analyzed SARS-CoV-2 infections and their impact on cancer in COVID-19 vaccinated and non-vaccinated patients from three German cancer centers. Overall, 133 patients with SARS-CoV-2 were enrolled in pre- and post-vaccine eras: 84 non-vaccinated and 49 vaccinated, respectively. A mild course of COVID-19 was documented more frequently in vaccinated patients (49% vs. 29%), while the frequency of severe and critical courses occurred in approximately one-half of the non-vaccinated patients (22% vs. 42%, p = 0.023). Particularly, patients with hematologic neoplasms benefited from vaccination in this context (p = 0.031). Admissions to intermediate- and intensive-care units and the necessity of non-invasive and invasive respiratory support were reduced by 71% and 50% among vaccinated patients, respectively. The median length of admission was 11 days for non-vaccinated and 5 days for vaccinated patients (p = 0.002). COVID-19 mortality was reduced by 83% in vaccinated patients (p = 0.046). Finally, the median time from SARS-CoV-2 infection to restarting cancer therapy was 12 and 26 days among vaccinated and non-vaccinated groups, respectively (p = 0.002). Although this study does not have enough power to perform multivariate analyses to account for confounders, it provides data on COVID-19 in non-vaccinated and vaccinated cancer patients and illustrates the potential benefits of COVID-19 vaccines for these patients.

Objectives: A high-performance liquid chromatography (HPLC) with mass spectrometry (MS) detection method was developed to quantify several tyrosine kinase inhibitors (TKIs) and their relevant metabolites. This method is suitable for therapeutic drug monitoring (TDM) of alectinib, brigatinib, dabrafenib, lenvatinib, lorlatinib, osimertinib and trametinib in patients with solid tumors using volumetric absorptive microsampling (VAMS^®). Methods: The HPLC-MS system contained four pumps, a Turboflow HTLC CycloneTM 1.0 × 50 mm solid phase extraction column for analyte enrichment, and a Kinetex 2.6 µm C18 100Å, 100 × 3.0 mm column for analyte separation. An acetonitrile–water gradient was used for the separation, and the ions generated by ESI (+)-ionization were detected in single-ion mode. This method was validated according to recent European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines. Results: The accuracy and precision shown during method validation were within the acceptable limits for all analytes in plasma and whole blood. All analytes showed acceptable stability in both matrices for at least 28 days when stored at −21 °C. So far, 100 venous plasma and 94 capillary blood samples have been collected and analyzed. Conclusions: We developed a reliable method to quantify several TKIs from plasma and capillary blood, which is intended for TDM purposes in clinical practice.

Background: Despite recent advances in the treatment of locally advanced non-small cell lung cancer (NSCLC), most patients relapse after definitive chemoradiotherapy followed by durvalumab consolidation. Due to limited evidence on post-relapse management, no standard treatment approach has been established for this patient population. Objectives: The objective of this study was to evaluate real-world treatment strategies and clinical outcomes in patients with NSCLC who experienced disease recurrence after durvalumab consolidation. Design: This was a multicenter, retrospective cohort study conducted across 12 German lung cancer centers. Methods: A total of 145 patients with recurrent NSCLC following chemoradiotherapy and durvalumab consolidation were analyzed. Clinical, pathological, and treatment-related data were collected, including smoking status, histology, molecular testing, therapeutic sequences, and survival outcomes. Overall survival (OS) and progression-free survival (PFS) were estimated and compared across subgroups according to relapse characteristics and post-relapse treatment strategies. Multivariate analyses were performed to identify independent prognostic factors. Results: The median OS from initial diagnosis was 27.1 months (95% confidence interval (CI): 22.5–31.8). After relapse, median OS was 12.2 months (95% CI: 9.9–14.4), and median PFS was 7.1 months (95% CI: 5.7–8.4). Approximately 70% of patients received systemic therapy after relapse, including platinum-based chemotherapy (18.6%), single-agent chemotherapy (18.6%), immune checkpoint inhibitors with or without chemotherapy (28.3%), and targeted therapy (4.8%). Patients treated with immune checkpoint inhibitors or targeted therapies showed a numerical improvement in OS compared with chemotherapy alone, although this difference did not reach statistical significance. Multivariate analysis identified first-line post-relapse treatment, Eastern Cooperative Oncology Group performance status, and histologic subtype as independent prognostic factors for OS. Conclusion: Patients with relapsed NSCLC after durvalumab consolidation have a poor prognosis and remain a therapeutically underserved population. Clinical outcomes appear to be influenced by performance status, histology, and the choice of post-relapse therapy. Prospective clinical trials are urgently needed to define optimal treatment strategies for these patients.