Publications by authors named "N I Vokes"
Background: KRAS inhibitors are revolutionizing the treatment of NSCLC, but clinico-genomic determinants of treatment efficacy warrant continued exploration.
Methods: Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib (KRYSTAL-1-NCT03785249) were included in the analysis. Pre-treatment NGS data were collected per protocol.
Introduction: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are a recently defined group of aggressive cancers in which the effectiveness of standard treatments for lung cancer is unknown.
Methods: We collected clinical, pathologic, and demographic variables from five institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated phenotype and loss of SMARCA4 (BRG1) by immunohistochemistry).
Results: We identified 92 patients with SMARCA4-UTs; 58 (63%) had stage IV disease at diagnosis and 16 (17%) developed recurrent or metastatic disease after initial diagnosis.
Introduction: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.
Methods: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869).
Article Synopsis
- Approximately 10% of lung adenocarcinomas (LUAD) have mucinous histology (LUADMuc), which is linked to a lighter/absent smoking history and a higher prevalence of KRAS mutations compared to LUAD without this histology (LUADnon-muc).
- A study analyzed features and treatment outcomes of LUADMuc and LUADnon-muc patients, revealing LUADMuc patients had less aggressive disease characteristics and a poorer response to current therapies, especially immunotherapy.
- Overall, LUADMuc showed lower objective response rates, shorter progression-free and overall survival compared to LUADnon-muc, highlighting a need for more effective treatment strategies for this subgroup.
Article Synopsis
- The introduction of immune checkpoint blockade (ICB) has greatly improved treatment outcomes for advanced melanoma, but many patients still become resistant to it due to unclear reasons.
- Although combining different ICB therapies has been shown to enhance response rates, it also comes with increased toxicity for patients.
- An analysis of tumor samples from ICB-naïve patients revealed that high genomic heterogeneity and low ploidy can identify those who are intrinsically resistant to aPD-1, leading to a predictive model that may help tailor treatment strategies.