A comparative study of the efficacy and safety of PD-1/L1 inhibitor and platinum-containing dual-agent chemotherapy in patients with advanced non-small cell lung cancer resistant to EGFR-TKIs.

To assess the efficacy and safety of combining Programmed Death-1/Programmed Death-Ligand 1 (PD-1/L1) inhibitors with platinum-containing chemotherapy for treating late-stage Non-Small Cell Lung Cancer (NSCLC) patients who have developed resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs). A retrospective analysis was conducted at Baoji Traditional Chinese Medicine Hospital involving 133 patients with advanced NSCLC who had shown resistance to EGFR-TKIs and were treated from October 2018 to May 2021. The cohort was categorized into two groups: one treated with immune checkpoint inhibitors (ICIs) plus chemotherapy and antiangiogenic agents (ICIs+BCP group), and the other treated with ICIs alone (ICIs group). Baseline data collected included demographic factors, smoking status, PD-L1 Tumor Proportion Score (TPS), EGFR mutation, Eastern Cooperative Oncology Group (ECOG) score, and routine blood markers prior to second-line therapy. Computed Tomography (CT) scans were performed every two treatment courses to evaluate the treatment efficacy. The ICIs+BCP group exhibited a statistically significant improvement in Overall Survival (OS) compared to the ICIs group (P=0.001). Cox survival analysis uncovered age (P=0.012), PD-L1 TPS expression (P<0.001), treatment regimen (P=0.006), Neutrophil-to-Lymphocyte Ratio (NLR) (P=0.024), and Platelet-to-Lymphocyte Ratio (PLR) (P=0.005) as independent factors influencing OS in patients with advanced NSCLC resistant to primary-line EGFR-TKI therapy. The nomogram model, based on these prognostic factors, exhibited Area Under the Curve (AUC) values of 0.823 and 0.769, indicating its predictive accuracy for 1-year and 2-year survival, respectively. Combining ICIs with BCP prolongs OS in patients with NSCLC resistant to EGFR-TKIs. This study underscores the importance of personalized treatment plans and biomarker evaluations to improve outcomes in drug-resistant cases.

Shi C ，Liu X ，Zhao J ，Xu W ，Zhang R ，He Z ... -  《American Journal of Translational Research》

Real-world study of PD-1/L1 immune checkpoint inhibitors for advanced non-small cell lung cancer after resistance to EGFR-TKIs.

Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) inhibitors have achieved good efficacy and safety in patients with advanced EGFR mutation-negative non-small cell lung cancer (NSCLC), but their efficacy in patients with previous EGFR mutations is limited. The aim of the present study was to explore the efficacy of PD-1/L1 immune checkpoint inhibitors for the treatment of patients with advanced NSCLC who are resistant to EGFR-TKIs. This retrospective study included 123 patients with stage IV NSCLC who received treatment in Shanghai Changzheng Hospital between January 2019 and January 2022 after failure of first-line EGFR-TKIs. Of them, 39 received ICIs + chemotherapy and anti-angiogenic drugs (ICIs+BCP group), 51 received ICIs monotherapy (ICIs group), and 33 received chemotherapy and anti-angiogenic drugs (BCP group). The gender, age, smoking history, ECOG score, EGFR mutation type, PD-L1 TPS expression, and the first routine blood index before second-line treatment of all enrolled patients were recorded, and their clinical outcomes and prognosis factors were analyzed. There was no significant difference in the objective response rate (ORR) and disease control rate (DCR) between the three groups. Patients in ICIs+BCP group had better prognosis than those in ICIs monotherapy group (PFS:9.5 vs. 4.64 months, p<0.001; OS: 16.97 vs. 7.9 months p<0.001) or BCP group (9.5 vs. 6.48 months, p<0.005; OS: 16.97 vs. 11.39 months p<0.005). Our findings suggest that in the real-world practice in China, PD-1/L1 immune checkpoint inhibitors combined with chemotherapy and anti-angiogenic drugs are effective for the treatment of patients with advanced NSCLC who are resistant to EGFR-TKIs.

Wei K ，Zhou C ，Chen Y ，Feng X ，Tang H ... -  《Frontiers in Oncology》

Efficacy of ICI-based treatment in advanced NSCLC patients with PD-L1≥50% who developed EGFR-TKI resistance.

Platinum-based chemotherapy is still the standard of care for Epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) patients after developing EGFR-TKI resistance. However, no study focusing on the role of immuno checkpoint inhibitor (ICI) based treatments for EGFR mutated NSCLC patients who carried programmed death ligand 1 (PD-L1) tumor proportion score (TPS) greater than 50% progressed after EGFR-TKI therapy. In this study, we retrospectively investigated the outcomes of ICI-based treatments for EGFR mutated NSCLC patients carried PD-L1 TPS≥50% after developing EGFR-TKI resistance and to explore the population that may benefited from ICI-based treatment. We retrospectively collected data of advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation at Shanghai Chest Hospital between January 2018 and June 2021. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of this study. A total of 146 patients were included. Up to June 20th, 2022, median follow-up was 36.7 months (IQR, 12.5-44.2 months). Among the population, 66 patients (45.2%) received chemotherapy, the remaning (54.8%) received ICI-based treatment, including 56 patients(70.0%) received ICI combined with chemotherapy (IC) and 24 patients (30.0%) received ICI monotherapy (IM). In IC group,31 patients received ICI combined with chemotherapy,19 patients received ICI combined with antiangiogenic therapy and remaing received ICI combined with chemotherapy and antiangiogenic therapy. Survival analysis shown that patients who received ICI-based treatment had better progress-free survival (PFS) and overall survival (OS) compared with those treated with other therapy (median PFS, 10.0 vs. 4.0 months, P<0.001; median OS, 39.5 vs. 24.2 months, P<0.001). What's more, patients who treated with IC treatment had a superior survival time than those received IM treatment (median PFS, 10.3 vs. 7.0 months, P<0.001; median OS, 41.6 vs. 32.4 months, P<0.001). Subgroup analysis found that the PFS and OS benefit of IC was evident in all subgroups. For advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation, ICI-based treatment could provide a more favorable survival than classical chemotherapy. What' s more, compared with ICI monotherapy, ICI combined with chemotherapy seems to be the preferred treatment.

Li Y ，Jiang H ，Qian F ，Chen Y ，Zhou W ，Zhang Y ，Lu J ，Lou Y ，Han B ，Zhang W ... -  《Frontiers in Immunology》

[A Real-world Study on the Expression Characteristics of PD-L1 in Patients 
with Advanced EGFR Positive NSCLC and Its Relationship with the 
Therapeutic Efficacy of EGFR-TKIs].

Chen R ，Gao X ，Xu F ，Zhang S ，Ma L ，Hu B ... -  《-》

Epidermal Growth Factor Receptor Mutation (EGFR) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor (TKI) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer: An Evidence-Based Analysis.

Medical Advisory Secretariat 《-》