Researchers conducted a subgroup analysis of POSEIDON trial data, then characterized underlying biologic mechanisms using mouse models.
Adding a second checkpoint inhibitor to chemotherapy improves outcomes among patients with non–small cell lung cancer who haveThese findings, drawn from a post hoc analysis of phase 3 data, are backed up by cell line and mouse data revealing clear mechanisms of efficacy, making the collective evidence compelling enough to reshape clinical practice, reported lead authormutations are associated with limited benefit from PD-1 or PD-L1 inhibition, the association between these mutations and benefit...
This was first observed in the objective response rate, which was 42.9% with dual checkpoint blockade plus chemotherapy vs 30.2% with single checkpoint blockade plus chemotherapy and 28% for chemotherapy alone. Durations of response improved in kind. “These data support the hypothesis that CTLA-4 inhibition can mitigate the resistance to chemotherapy plus PD-1 inhibition observed in patients who havemutations and suggest that this group of patients derives greater benefit from CTLA-4 inhibition than do patients who lack either alteration,” Skoulidis and colleagues wrote.
Dual checkpoint blockade reprogrammed the immune microenvironment, leading to increased activation of CD4+ T helper cells, specifically the Th1 subtype, while inducing tumoricidal changes in myeloid cells. Consequently, antitumor responses improved, resulting in tumor regression and prolonged survival, compared with PD-1 monotherapy.
Lung Carcinoma Cancer Of The Lung Chemotherapy Non-Small Cell Lung Cancer Nsclc Biologic Therapy Biologics Tumor Cancer Malignant Neoplasia Carcinoma Malignant Neoplasm Small Cell Lung Cancer Small-Cell Lung Cancer Oat Cell Lung Cancer SCLC Toxicology Toxicity Poisoning Toxins Biomarker Biological Marker Multi-Biomarker Disease Activity MBDA
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