Resected NSCLC Research Articles

Prognostic Impact of Adjuvant Immunotherapy in Patients With Resectable NSCLC After Neoadjuvant Chemoimmunotherapy: A Brief Report

ObjectiveThe potential survival benefits of adjuvant immunotherapy for resectable NSCLC after neoadjuvant chemoimmunotherapy, and the optimal number of adjuvant immunotherapy cycles, remain uncertain. This study aims to evaluate the prognostic impact of adjuvant immunotherapy and determine the optimal number of cycles. MethodsA total of 438 patients who received neoadjuvant chemoimmunotherapy between August 2019 and June 2022 across four hospitals were enrolled in this study, with a median follow-up time of 31.3 months. Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier methods and tested by log-rank test. Unstratified Cox proportional hazards models were fitted to the subgroups. ResultsIn this multi-center cohort, 29.7% of patients (n = 130) achieved a pathologic complete response. Patients who received adjuvant immunotherapy experienced significant survival benefits compared with those who did not (RFS: hazard ratio [HR] = 0.63, 95% confidence interval: 0.41–0.98, p = 0.037; OS: hazard ratio = 0.27, 95% confidence interval: 0.13–0.57, p < 0.001). Subgroup analyses found that patients with a squamous histologic type, positive PD-L1 expression, and those with a major pathologic response particularly benefited from adjuvant immunotherapy. In addition, we found that six cycles of adjuvant immunotherapy served as a threshold for better prognostic differentiation, suggesting that six or more cycles may be more beneficial. ConclusionsOur study found that the addition of adjuvant immunotherapy to neoadjuvant chemoimmunotherapy is significantly associated with improved RFS and OS in patients with resectable NSCLC. We also identified that six cycles of adjuvant immunotherapy may be the optimal regimen for these patients.

Real-World Clinical Outcomes of Neoadjuvant Platinum-Based Chemotherapy with Nivolumab in Non-Small Cell Lung Cancer.

Background: Lung cancer is among the most prevalent and serious forms of cancer, characterized by an allogenic phenotype that presents significant therapeutic challenges. Materials and Methods: We analyzed medical records from January 2022 to August 2023, focusing on individuals aged 18 and older diagnosed with resectable NSCLC who received neoadjuvant chemo-immunotherapy prior to surgical intervention. Results: The cohort comprised 56 patients, predominantly smokers (95%) and male (74%), with 80% presenting the disease at stage III. Of the participants, 44 underwent surgery, with 95% receiving lobar resection. Clinical assessments via PET-CT imaging revealed an 86% rate of response or disease stabilization, while pathological evaluations showed complete and major pathological responses in 61% of cases. Conclusions: This real-world data supports the safety and efficacy of incorporating immune checkpoint inhibitors in the neoadjuvant treatment of NSCLC, followed by surgical resection.

Perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy for resectable non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 2 trial (TD-NeoFOUR trial)

This open-label, single-arm, phase 2 trial evaluated the efficacy and safety of neoadjuvant sintilimab combined with anlotinib and chemotherapy, followed by adjuvant sintilimab, for resectable NSCLC. Forty-five patients received anlotinib (10 mg, QD, PO, days 1–14), sintilimab (200 mg, day 1), and platinum-based chemotherapy of each three-week cycle for 3 cycles, followed by surgery within 4–6 weeks. Adjuvant sintilimab (200 mg) was administered every 3 weeks. The primary endpoint was achieving a pathological complete response (pCR). From June 10, 2021 through October 10, 2023, 45 patients were enrolled and composed the intention-to-treat population. Twenty-six patients (57.8%) achieved pCR, and 30 (66.7%) achieved major pathological response (MPR). Forty-one patients underwent surgery. In the per-protocol set (PP set), 63.4% (26/41) achieved pCR, and 73.2% achieved MPR. The median event-free survival was not attained (95% CI, 25.1-NE). During the neoadjuvant treatment phase, grade 3 or 4 treatment-related adverse events were observed in 25 patients (55.6%), while immune-related adverse events were reported in 7 patients (15.6%). We assessed vascular normalization and infiltration of immune-related cells by detecting the expression of relevant cell markers in NSCLC tissues with mIHC. Significant tumor microenvironment changes were observed in pCR patients, including reduced VEGF+ cells and CD4+Foxp3+ Treg cells, and increased perivascular CD4+ T cells, CD39+CD8+ T cells, and M1 macrophages. In conclusion, perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy achieved pCR in a notable proportion of patients with resectable NSCLC and were associated with profound changes in the tumour microenvironment (ClinicalTrials.gov NCT05400070).

OA01.05 Neoadjuvant Nivolumab with or without Relatlimab in Resectable NSCLC: Additional Analysis and Extended Follow-up

OA01.05 Neoadjuvant Nivolumab with or without Relatlimab in Resectable NSCLC: Additional Analysis and Extended Follow-up

OA13.03 Perioperative Durvalumab for Resectable NSCLC (R-NSCLC): Updated Outcomes from the Phase 3 AEGEAN Trial

OA13.03 Perioperative Durvalumab for Resectable NSCLC (R-NSCLC): Updated Outcomes from the Phase 3 AEGEAN Trial

P4.07D.03 Phase 2 Peri-Operative Study of Fianlimab+Cemiplimab+Chemotherapy vs Cemiplimab+Chemotherapy in Resectable Early-Stage NSCLC

P4.07D.03 Phase 2 Peri-Operative Study of Fianlimab+Cemiplimab+Chemotherapy vs Cemiplimab+Chemotherapy in Resectable Early-Stage NSCLC

P1.06B.18 Pathologic Response Assessment of Resected NSCLC Neoadjuvant Therapy Specimens with Tumor Size Larger Than 3cm by Different Sampling Methods

P1.06B.18 Pathologic Response Assessment of Resected NSCLC Neoadjuvant Therapy Specimens with Tumor Size Larger Than 3cm by Different Sampling Methods

P2.07C.01 LCMC3: Clinical Utility of Suvmax on Preoperative 18F-FDG PET-CT in Resectable NSCLC Treated with Neoadjuvant Atezolizumab

P2.07C.01 LCMC3: Clinical Utility of Suvmax on Preoperative 18F-FDG PET-CT in Resectable NSCLC Treated with Neoadjuvant Atezolizumab

P1.06C.05 The Impact of Lymphovascular Invasion as Prognostic Factor on Long-Term Survival in More Than 3500 Resected NSCLC Patients

P1.06C.05 The Impact of Lymphovascular Invasion as Prognostic Factor on Long-Term Survival in More Than 3500 Resected NSCLC Patients

PD-L1+ Lymphocytes Are Associated with CD4+, Foxp3+CD4+, IL17+CD4+ T Cells and Subtypes of Macrophages in Resected Early-Stage Non-Small Cell Lung Cancer.

The non-canonical PD-L1 pathway revealed that programmed-death ligand 1 (PD-L1) expression in immune cells also plays a crucial role in immune response. Moreover, immune cell distribution in a tumour microenvironment (TME) is pivotal for tumour genesis. However, the results remain controversial and further research is needed. Distribution of PD-L1-positive (PD-L1+) tumour-infiltrating lymphocytes in the context of TME was assessed in 72 archival I-III stage surgically resected NSCLC tumour specimens. Predominant PD-L1+ lymphocyte distribution in the tumour stroma, compared to islets, was found (p = 0.01). Higher PD-L1+ lymphocyte infiltration was detected in smokers due to their predominance in the stroma. High PD-L1+ lymphocyte infiltration in tumour stroma was more common in tumours with higher CD4+ T cell infiltration in islets and stroma, Foxp3+CD4+ T cell infiltration in islets and lover M1 macrophage infiltration in the stroma (p = 0.034, p = 0.034, p = 0.005 and p = 0.034 respectively). Meanwhile, high PD-L1+ lymphocyte infiltration in islets was predominantly found in tumours with high levels of IL-17A+CD4+ T cells in islets and Foxp3+CD4+ T cells in islets and stroma (p = 0.032, p = 0.009 and p = 0.034, respectively). Significant correlations between PD-L1+ lymphocytes and tumour-infiltrating CD4+, Foxp3+CD4+, IL-17A+CD4+ T cells and M2 macrophages were found. An analysis of the tumour-immune phenotype revealed a significant association between PD-L1 expression and IL17+CD4+ and Foxp3+CD4+ immune phenotypes. PD-L1+ lymphocytes are associated with the distribution of CD4+, Foxp3+CD4+, IL17A+CD4+ T cells, M1 and M2 macrophages in TME of resected NSCLC.

Improved Event-Free Survival After Complete or Major Pathologic Response in Patients With Resectable NSCLC Treated With Neoadjuvant Chemoimmunotherapy Regardless of Adjuvant Treatment: A Systematic Review and Individual Patient Data Meta-Analysis

IntroductionNeoadjuvant chemoimmunotherapy has reshaped the treatment landscape for resectable NSCLC, yet the prognostic significance of pathologic response remains unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis to evaluate the impact of achieving pathologic complete response (pCR) or major pathologic response (MPR) on event-free survival (EFS) and assessed the influence of adjuvant immunotherapy. MethodsWe performed an IPD meta-analysis of prospective clinical trials on neoadjuvant or perioperative anti–programmed death-ligand 1 in combination with platinum-based chemotherapy in patients with resectable NSCLC. The IPD was extracted from Kaplan-Meier curves for pCR and MPR from the included studies. Survival outcomes were compared between patients achieving pCR or MPR and those who did not, considering both intention-to-treat and resected populations. ResultsAchieving pCR or MPR was associated with improved EFS in the intention-to-treat population (pCR, hazard ratio = 0.13; MPR, hazard ratio = 0.18, respectively) with a 24 months EFS rate of 94% and 88% for patients who achieved pCR and MPR, respectively. Independently from pCR status, patients who were treated in an experimental arm that included adjuvant immunotherapy had similar EFS. ConclusionsOur study reported a strong EFS improvement in patients who achieved either pCR or MPR after neoadjuvant chemoimmunotherapy. The use of adjuvant immunotherapy after tumor resection was not associated with improved EFS.

Resectable Non-Small Cell Lung Cancer Heterogeneity and Recurrence Assessed by Tissue Next-Generation Sequencing Genotyping and Circulating Tumor Cell EZH2 Characterization

IntroductionNon-small cell lung cancer (NSCLC) is the most common type of lung neoplasm. Despite surgical resection, it has a high relapse rate, accounting for 30–55% of all cases. Next-generation sequencing (NGS) based on a customized gene panel and the analysis of circulating tumor cells (CTCs) can help identify heterogeneity, stratify high-risk patients, and guide treatment decisions. In this descriptive study involving a small prospective cohort, we focus on the phenotypic characterization of CTCs, particularly concerning EZH2 expression (a member of the Polycomb Repression Complex 2), as well as on the mutation profiles of the tissue using a customized gene panel and their association with poor outcomes in NSCLC. MethodsIsolation and characterization of EZH2 on CTCs were evaluated before surgical resection (CTC1) and one month after surgery (CTC2) in resectable NSCLC patients. Targeted NGS was performed using a customized 50-gene panel on tissue samples from a subset of patients. Results76 patients with resectable NSCLC were recruited. The top mutated genes in the cohort included TP53, FLT1, MUC5AC, EGFR, and NLRP3. Pair of genes that had mutually exclusive mutations was TP53-RIN3, and pairs of genes with co-occurring mutations were CD163-TLR4, FGF10-FOXP2, ADAMTSL3-FLT1, ADAMTSL3-MUC5AC and MUC5AC-NLRP3. CTCs decreased significantly between the two time points CTC1 and CTC2 (p<0.0001), and CTCs+ patients with high EZH2 expression had an 87% increased risk of death (p=0.018). ConclusionsIntegrating molecular profiling of tumors and CTC characterization can provide valuable insights into tumor heterogeneity and improve patient stratification for resectable NSCLC.

MA01.12 Survival Outcomes and Pathologic Response after Chemo-Immunotherapy in Resectable NSCLC: An Individual Patient Data Meta-Analysis

MA01.12 Survival Outcomes and Pathologic Response after Chemo-Immunotherapy in Resectable NSCLC: An Individual Patient Data Meta-Analysis

PL02.07 Neocoast-2: Efficacy and Safety of Neoadjuvant Durvalumab (D) + Novel Anticancer Agents + CT and Adjuvant D ± Novel Agents in Resectable NSCLC

PL02.07 Neocoast-2: Efficacy and Safety of Neoadjuvant Durvalumab (D) + Novel Anticancer Agents + CT and Adjuvant D ± Novel Agents in Resectable NSCLC

L’immunothérapie péri-opératoire des cancers bronchiques non à petites cellules (CBNPC) : standards actuels et perspectives

Surgery is the cornerstone of the treatment for stage I to IIIA NSCLC. Perioperative platinum-based chemotherapy has long been combined with surgery for patients with resectable stage II-IIIA disease, although the benefits are modest, with an increase in overall survival of approximately 5 %. Recently, immunotherapy has been integrated into neo-adjuvant, adjuvant, and perioperative treatment regimens based on data demonstrating improved event-free survival (EFS) and disease-free survival (DFS), respectively, for localized or locally advanced resectable NSCLC, without activating mutation. Two phase 3 trials have shown an adjuvant benefit and have been approved in Europe but are not supported in France. Four phase III trials Checkmate-816, Checkmate-77T, AEGEAN and KEYNOTE-671 showed a benefit from the combination of an immune checkpoint inhibitor with chemotherapy in the neoadjuvant or in perioperative setting. The results of Checkmate-816 enabled the early access authorization of Nivolumab, in combination with platinum-based chemotherapy in the neoadjuvant treatment of adult patients with resectable NSCLC at high risk of recurrence, including tumors express PD-L1 at the threshold ≥ 1 %, not EGFR mutated, nor ALK translocated.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

P4.07F.03 A Cost-Effective Tumor-Informed ctDNA Analysis for MRD Detection in Resected NSCLC With Common Driver Genes

P4.07F.03 A Cost-Effective Tumor-Informed ctDNA Analysis for MRD Detection in Resected NSCLC With Common Driver Genes

EP.07C.11 Adjuvant Immunotherapy for Patients with Resectable NSCLC after Pathologic Complete Response

EP.07C.11 Adjuvant Immunotherapy for Patients with Resectable NSCLC after Pathologic Complete Response

P3.08F.07 Efficacy and Safety of Envafolimab Plus Platinum-based Chemotherapy as Neoadjuvant Therapy in Resectable Stage II-IIIB NSCLC

P3.08F.07 Efficacy and Safety of Envafolimab Plus Platinum-based Chemotherapy as Neoadjuvant Therapy in Resectable Stage II-IIIB NSCLC

EP.07H.01 Analysis of Variables Predicting pCR and irAEs in Resectable NSCLC Receiving Neoadjuvant Immunotherapy with Chemotherapy (Pre-PLaN)

EP.07H.01 Analysis of Variables Predicting pCR and irAEs in Resectable NSCLC Receiving Neoadjuvant Immunotherapy with Chemotherapy (Pre-PLaN)

MA15.07 Preliminary Analysis of Adjuvant Chemotherapy with Atezolizumab in Stage I-III Resected NSCLC and Clearance of ctDNA

MA15.07 Preliminary Analysis of Adjuvant Chemotherapy with Atezolizumab in Stage I-III Resected NSCLC and Clearance of ctDNA