Immunotherapy has transformed the lung cancer treatment landscape, establishing a role in nearly all histologic subtypes, including non-small cell and small cell lung cancers. However, only a few biomarkers, including PD-L1 tumor proportion score, tumor mutational burden, and microsatellite instability, are currently available, and their predictive value remains inconsistent across different histologies. The biological heterogeneity of lung tumors and the dynamic interplay between systemic therapies and the tumor microenvironment (TME) further complicate biomarker development. At the same time, novel immunotherapeutic strategies, including bispecific antibodies and antibody-drug conjugates, are expanding the spectrum of immune targets beyond conventional checkpoint inhibition, highlighting the need for biomarkers that better reflect the functional state of the TME. In this review, we address the limitations of currently used biomarkers across lung cancer histologies and describe emerging immune-related biomarkers encompassing innate immune infiltration, antigen presentation capacity, cytotoxic T-cell activation, and inflammatory signaling; these have shown promise as histology-independent predictors of response. Robust prospective studies are essential to validate integrated signatures capable of capturing profiles of patients who are most likely to respond to immune checkpoint inhibitors and next-generation treatments.
E. Gobbini, Subhamoy Chakraborty, I. Vathiotis et al.· Cancer immunology research· 0 citations
Background Extensive-disease small-cell lung cancer (ED-SCLC) is an aggressive disease with limited effective therapeutic options. Clinical trials suggest an additive effect of chemotherapy and immunotherapy in SCLC, although the magnitude of benefit seems to be limited. Considering the prolonged peripheral persistence of anti-PD-(L)1 blockade, we wanted to investigate the impact of prior immunotherapy exposure on the efficacy of second-line chemotherapy. Patients and methods Using the Epidemio-Strategy and Medical Economics lung cancer national real-world database, we selected ED-SCLC patients diagnosed between 17 February 2010 and 4 December 2023 who had received at least two lines of treatment for a metastatic disease with platinum-based regimens in the first-line setting. Second-line real-world progression-free survival (rw-PFS) and overall survival (OS) were analyzed according to first-line immunotherapy exposure using a multivariable Cox proportional hazards model and a propensity score-weighted sensitivity analysis. Results The study included 2051 patients with ED-SCLC: 638 (30%) in the immunotherapy-pretreated group and 1413 (70%) who received only first-line chemotherapy. Multivariable analysis showed no significant difference in second-line median rw-PFS between immunotherapy-pretreated patients [2.9 months, 95% confidence interval (CI) 2.7-3.3] and chemotherapy-only pretreated patients (2.5 months, 95% CI 2.4-2.7) (hazard ratio 0.94, 95% CI 0.85-1.04, P = 0.21). Similar results were observed in the propensity score adjusted Cox regression sensitivity analysis. A longer median OS from the start of second-line treatment was observed in immunotherapy-pretreated patients (6.6 months, 95% CI 6.1-7.1 compared with 5.7 months, 95% CI 5.4-6.1, P = 0.03) although, this result has not been confirmed in a more contemporary cohort. Conclusion This study showed no OS gain in second-line treatment among patients pretreated with immunotherapy compared with those who received chemotherapy alone as first-line treatment.
E. Gobbini, M. H. Diallo, C. Clément-Duchêne et al.· ESMO Open· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
