Advanced NSCLC Patients Research Articles

Uncovering the role of tumor cGAS expression in predicting response to PD-1/L1 inhibitors in non-small cell lung cancer

ObjectivesThe impact of cGAS/STING tumor expression on PD-1/L1 inhibitor efficacy and the tumor microenvironment remain to be elucidated.MethodsIn a post-hoc analysis of a prospective biomarker study with 106 advanced NSCLC patients treated with PD-1/L1 inhibitors from December 2015 to September 2018, tumor tissue before treatment from 68 patients was analyzed. cGAS and STING expression were measured using immunohistochemical staining and H-scores. Additionally, 40 serum proteins were quantified before and 4–6 weeks after treatment initiation.ResultsMedian cGAS and STING H-scores were 220 (range, 5–300) and 190 (range, 0–300), respectively. There were no differences in cGAS or STING H-scores between the high (tumor proportion score [TPS] ≥ 50) and low (TPS < 50) PD-L1groups (p = 0.990 and 0.283, respectively). Unexpectedly, patients with high cGAS (H-score ≥ 220) demonstrated significantly shorter progression-free survival (PFS) of PD-1/L1 inhibitors when the PD-L1 TPS was high (median PFS: 143 days vs. not reached; p = 0.028); PFS at 18 months was 7% and 53% in the high and low cGAS groups, respectively while STING expression did not impact PFS. In serum protein analyses, high cGAS H-score was associated with significantly higher TGF-β1 and TGF-β2 before PD-1/L1 inhibition (47.5 vs. 22.3 ng/l, p = 0.023; 2118 vs. 882 pg/ml, p = 0.037); additionally, the cGAS H-score significantly correlated with TGF-β1 (r = 0.451, p = 0.009) and TGF-β2 (r = 0.375, p = 0.031) basal levels.ConclusioncGAS expression, but not STING, predicts poor PD-1/L1 inhibitor efficacy in NSCLC with high PD-L1, potentially due to a TGF-β-mediated immunosuppressive environment (UMIN000024414).

Efficacy of Atezolizumab in Subsequent Lines of Therapy for NSCLC Patients: Insights from Real-World Data.

This retrospective study involved 147 advanced NSCLC patients treated with atezolizumab following progression on prior platinum-based chemotherapy at two academic centers in Serbia. Data on demographics and clinical, pathological, and molecular characteristics were collected. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards regression identified outcome predictors. The median PFS was 7.13 months, and median OS was 38.6 months. The overall response rate (ORR) was 15%, with a disease control rate (DCR) of 57.9%. No significant PFS differences were observed between patients treated with atezolizumab in the second line versus later lines. Patients with good performance status (ECOG 0-1) had significantly better PFS compared to those with poorer status (12.03 vs. 1.63 months, p < 0.0001). Atezolizumab is effective in both second-line and later-line settings for advanced NSCLC, particularly in patients with good performance status. This highlights the importance of patient selection based on performance status, as well as the need for wider access to ICIs in resource-limited regions.

OA11.06 Cemiplimab Monotherapy for First Line Advanced NSCLC Patients with PD-L1 Expression ≥50%: 5-y Outcomes of EMPOWER-Lung 1

OA11.06 Cemiplimab Monotherapy for First Line Advanced NSCLC Patients with PD-L1 Expression ≥50%: 5-y Outcomes of EMPOWER-Lung 1

EP.06F.06 Concurrent DNA and RNA NGS Testing to Characterize Rare Fusions in Advanced NSCLC Patients

EP.06F.06 Concurrent DNA and RNA NGS Testing to Characterize Rare Fusions in Advanced NSCLC Patients

EP.11A.13 Efficacy and Safety of Immune-Checkpoint Inhibitors in Advanced NSCLC Patients with Rare Mutation after Developing Targeted Therapy Resistance

EP.11A.13 Efficacy and Safety of Immune-Checkpoint Inhibitors in Advanced NSCLC Patients with Rare Mutation after Developing Targeted Therapy Resistance

P4.11E.26 A Multicenter Retrospective Study Reveals High MET Expression Associated with Superior Benefit from Immunotherapy in Advanced NSCLC Patients

P4.11E.26 A Multicenter Retrospective Study Reveals High MET Expression Associated with Superior Benefit from Immunotherapy in Advanced NSCLC Patients

P4.15E.03 Assessing the Utilization of Palliative Care in Advanced NSCLC Patients with Brain Metastases

P4.15E.03 Assessing the Utilization of Palliative Care in Advanced NSCLC Patients with Brain Metastases

P1.06B.11 Plasma MicroRNAs Profiling to Monitor Immunotherapy Response in Advanced NSCLC Patients

P1.06B.11 Plasma MicroRNAs Profiling to Monitor Immunotherapy Response in Advanced NSCLC Patients

P4.11E.22 Treatment-Free Survival in Advanced NSCLC Patients who Terminated Immune-Checkpoint Inhibitors.

P4.11E.22 Treatment-Free Survival in Advanced NSCLC Patients who Terminated Immune-Checkpoint Inhibitors.

Elucidating the role of baseline and on-treatment nutritional status and body composition on clinical outcomes in advanced nsclc patients treated with immunotherapy

Elucidating the role of baseline and on-treatment nutritional status and body composition on clinical outcomes in advanced nsclc patients treated with immunotherapy

P3.06E.04 Genetic and Immunological Backgrounds in Advanced NSCLC Patients Treated with Immunotherapy - NGS and Flow Cytometry Analysis

P3.06E.04 Genetic and Immunological Backgrounds in Advanced NSCLC Patients Treated with Immunotherapy - NGS and Flow Cytometry Analysis

Clinical Outcomes of Maintenance Durvalumab After Definitive Concurrent Chemoradiotherapy in Unresectable Locally Advanced Stage III NSCLC According to EGFR and ALK Status: Korean Cancer Study Group LU-22-18

IntroductionThe role of maintenance durvalumab after definitive concurrent chemoradiotherapy (CCRT) in unresectable locally advanced NSCLC with EGFR mutation or ALK translocation remains unclear. We compared the effectiveness of durvalumab maintenance therapy in groups with EGFR/ALK wild-type versus those with EGFR or ALK mutations. MethodsIn this retrospective multicenter observational study, patients with locally advanced NSCLC without progression after CCRT followed by maintenance durvalumab and available molecular test results (EGFR and ALK) were eligible. The primary objective was to compare progression-free survival (PFS) between EGFR/ALK wild-type and EGFR or ALK mutant NSCLC. Secondary objectives include overall survival according to EGFR or ALK mutation and programmed death-ligand 1 (PD-L1) expression. ResultsAmong 339 patients, 279 had wild-type EGFR/ALK, 41 had EGFR mutations and 19 had ALK translocations. The median age was 68 years with 276 male individuals (81.4%) and 63 female individuals (18.6%), 165 (49.3%) had adenocarcinoma, 149 (44.5%) had squamous cell carcinoma, and 21 (6.3%) had other histologic types, 120 (35.4%) had stage IIIA, 168 (49.6%) stage IIIB, and 51 (15.0%) had stage IIIC. Most of the patients (n = 288, 85%) achieved partial response to CCRT, two (0.6%) had a complete response, and 49 patients (14.4%) had stable disease. Excluding four patients with unknown PD-L1 tumor proportion score (TPS), 16 (4.8%) had a PD-L1 TPS of 0, 168 (50.1%) had 1 to 49, and 151 (45.1%) had 50 or higher. The median PFS was 21.4 months (95% confidence interval [CI]: 17.3–25.3) for the EGFR/ALK wild-type group and 21.0 months (95% CI: 15.7–not available [NA]) for the EGFR or ALK mutant group with no significant difference (p = 0.74). Significant differences occurred in PFS on the basis of PD-L1 expression with values of 13.6 (95% CI: 10.5–NA), 18.7 (95% CI: 15.1–26.9), and 24.7 (95% CI: 20.7–NA) months for TPS of 0, 1–49, and 50 or higher, respectively (p = 0.02). ConclusionsDurvalumab maintenance therapy after definitive CCRT in unresectable locally advanced NSCLC patients with EGFR or ALK mutation demonstrates comparable clinical outcomes to those with wild-type EGFR/ALK when PD-L1 expression is present.

EP.12E.01 OBX02-011, a Novel Oral ALK and EGFR Dual-target Tyrosine Kinase Inhibitor for the Treatment of Advanced NSCLC Patients

EP.12E.01 OBX02-011, a Novel Oral ALK and EGFR Dual-target Tyrosine Kinase Inhibitor for the Treatment of Advanced NSCLC Patients

Novel Combination of Therapeutic Approaches in Advanced NSCLC with EGFR Activating Mutations

The vast majority of advanced NSCLC cases are histologically represented by adenocarcinomas. EGFR activating mutations (exon 19 deletions, exon 21 L858R substitutions, exon 20 insertions) represent one of the most common druggable alterations. Since erlotinib’s FDA approval in 2013, EGFR-TKIs have represented a staple of EGFR+ advanced NSCLC treatment, with osimertinib representing the latest major FDA-approved third-generation EGFR-TKI. In recent years, however, several preclinical data have highlighted promising results regarding combination therapies involving EGFR-TKIs plus chemotherapy, and various recent clinical trials have confirmed these results. In addition, in 2021, amivantamab was the first FDA-approved mAb for the treatment of EGFR+ advanced NSCLC patients; according to some extremely up-to-date clinical trials, the combination of amivantamab plus chemotherapy is also associated with superior results. Therefore, this paper aims to provide a comprehensive review of both the bases and the latest evidence of the combination therapies involving EGFR+ advanced NSCLC patients.

1495P Impact of social isolation on the clinical outcomes in advanced NSCLC patients

1495P Impact of social isolation on the clinical outcomes in advanced NSCLC patients

1285P Deep learning prediction of response to advanced-generation ALK inhibitors (aALKi) in ALK-rearranged advanced NSCLC (aNSCLC) patients using digital pathology

1285P Deep learning prediction of response to advanced-generation ALK inhibitors (aALKi) in ALK-rearranged advanced NSCLC (aNSCLC) patients using digital pathology

1296P A phase II study to evaluate the efficacy and safety of BB-1701 in advanced or metastatic NSCLC patients with HER2 mutation/amplification

1296P A phase II study to evaluate the efficacy and safety of BB-1701 in advanced or metastatic NSCLC patients with HER2 mutation/amplification

1386P Prognostic value of EGFR A859S alteration in advanced NSCLC patients treated with third-generation EGFR-TKI

1386P Prognostic value of EGFR A859S alteration in advanced NSCLC patients treated with third-generation EGFR-TKI

1263P Biomarker analysis of plasma samples in YAMATO study: A randomized phase II trial comparing switching treatment of osimertinib following 8 months of afatinib (A) and osimertinib alone (B) in untreated advanced NSCLC patients with common EGFR mutation (TORG1939/WJOG12919L)

1263P Biomarker analysis of plasma samples in YAMATO study: A randomized phase II trial comparing switching treatment of osimertinib following 8 months of afatinib (A) and osimertinib alone (B) in untreated advanced NSCLC patients with common EGFR mutation (TORG1939/WJOG12919L)

Identification of a Proteomic Signature for Predicting Immunotherapy Response in Patients With Metastatic Non-Small Cell Lung Cancer

Immunotherapy has improved survival rates in patients with cancer, but identifying those who will respond to treatment remains a challenge. Advances in proteomic technologies have enabled the identification and quantification of nearly all expressed proteins in a single experiment. Integrating mass spectrometry with high-throughput technologies has facilitated comprehensive analysis of the plasma proteome in cancer, facilitating early diagnosis and personalized treatment. In this context, our study aimed to investigate the predictive and prognostic value of plasma proteome analysis using the SWATH-MS (Sequential Window Acquisition of All Theoretical Mass Spectra) strategy in newly diagnosed patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab therapy. We enrolled 64 newly diagnosed patients with advanced NSCLC treated with pembrolizumab. Blood samples were collected from all patients before and during therapy. A total of 171 blood samples were analyzed using the SWATH-MS strategy. Plasma protein expression in metastatic NSCLC patients prior to receiving pembrolizumab was analyzed. A first cohort (discovery cohort) was employed to identify a proteomic signature predicting immunotherapy response. Thus, 324 differentially expressed proteins between responder and non-responder patients were identified. In addition, we developed a predictive model and found a combination of seven proteins, including ATG9A, DCDC2, HPS5, FIL1L, LZTL1, PGTA, and SPTN2, with stronger predictive value than PD-L1 expression alone. Additionally, survival analyses showed an association between the levels of ATG9A, DCDC2, SPTN2 and HPS5 with progression-free survival (PFS) and/or overall survival (OS). Our findings highlight the potential of proteomic technologies to detect predictive biomarkers in blood samples from NSCLC patients, emphasizing the correlation between immunotherapy response and the idenfied protein set.