Outcome In Advanced Non-small Cell Lung Cancer Patients Research Articles

Predictive value of delta-radiomic features for prognosis of advanced non-small cell lung cancer patients undergoing immune checkpoint inhibitor therapy.

No robust predictive biomarkers exist to identify non-small cell lung cancer (NSCLC) patients likely to benefit from immune checkpoint inhibitor (ICI) therapies. The aim of this study was to explore the role of delta-radiomics features in predicting the clinical outcomes of patients with advanced NSCLC who received ICI therapy. Data of 179 patients with advanced NSCLC (stages IIIB-IV) from two institutions (Database 1 =133; Database 2 =46) were retrospectively analyzed. Patients in the Database 1 were randomly assigned into training and validation dataset, with a ratio of 8:2. Patients in Database 2 were allocated into testing dataset. Features were selected from computed tomography (CT) images before and 6-8 weeks after ICI therapy. For each lesion, a total of 1,037 radiomic features were extracted. Lowly reliable [intraclass correlation coefficient (ICC) <0.8] and redundant (r>0.8) features were excluded. The delta-radiomics features were defined as the relative net change of radiomics features between two time points. Prognostic models for progression-free survival (PFS) and overall survival (OS) were established using the multivariate Cox regression based on selected delta-radiomics features. A clinical model and a pre-treatment radiomics model were established as well. The median PFS (after therapy) was 7.0 [interquartile range (IQR): 3.4, 9.1] (range, 1.4-13.2) months. To predict PFS, the model established based on the five most contributing delta-radiomics features yielded Harrell's concordance index (C-index) values of 0.708, 0.688, and 0.603 in the training, validation, and testing databases, respectively. The median survival time was 12 (IQR: 8.7, 15.8) (range, 2.9-23.3) months. To predict OS, a promising prognostic performance was confirmed with the corresponding C-index values of 0.810, 0.762, and 0.697 in the three datasets based on the seven most contributing delta-radiomics features, respectively. Furthermore, compared with clinical and pre-treatment radiomics models, the delta-radiomics model had the highest area under the curve (AUC) value and the best patients' stratification ability. The delta-radiomics model showed a good performance in predicting therapeutic outcomes in advanced NSCLC patients undergoing ICI therapy. It provides a higher predictive value than clinical and the pre-treatment radiomics models.

Unleashing deep features and radiomics to enhance best overall response prediction to immunotherapy in advanced non-small cell lung cancer.

e20611 Background: Predicting immunotherapy response in advanced non-small cell lung cancer (NSCLC) through non-invasive means could be a groundbreaking advancement. Deep features extracted from medical images by deep Convolutional Neural Networks (CNNs) along with radiomics have demonstrated promising results in different oncologic diseases. However, the method for extracting these deep features influences the predictive capabilities of the model. Methods: A retrospective analysis of a multicenter study was conducted in advanced NSCLC patients with high PD-L1 expression with the aim of developing an imaging features-based model for the prediction of best overall response (BOR) to a checkpoint inhibitor immunotherapy. All visible lung lesions, beyond RECIST 1.1, were manually segmented in baseline CT scans. Radiomics features were extracted at lesion-level, and various preprocessing methods and CNN architectures were tested for deep features extraction. Radiomics and deep features were harmonized using ComBat methodology. A distinctive feature signature was created for each patient by calculating the mean across all lesions. Using this data, machine learning models were trained to predict treatment response, specifically distinguishing between complete response (CR) and partial response (PR) from stable disease (SD) and progressive disease (PD). The study compared the performance of different deep features extraction methods and assessed shapley additive explanations (SHAP) values of radiomics for interpretability. Results: In the cohort of 116 patients (mean age: 67, 93% ever-smokers, 73% male), 1024 to 5475 quantitative imaging features per lesion were extracted. Among these patients, 67 patients were CR+PR, and 49 were SD+PD. The top-performing predictive model, trained with radiomics and deep features from a deep convolutional autoencoder, achieved an average AUC of 85%. SHAP values showed that impactful radiomics features were correlated with intensity changes in adjacent pixels describing the tumor heterogeneity, along with shape features potentially associated with malignancy. Ultimately, combining both features demonstrated statistical significance, leading to a performance improvement of ~2-5% compared to models exclusively using deep features. Conclusions: Diverse techniques for extracting deep features were evaluated, revealing autoencoder training as the most effective strategy for predicting immunotherapy response. Consequently, the findings suggest that employing deep learning to extract imaging features from baseline CT scans, combined with radiomics, represents a promising non-invasive approach for the predicting immunotherapy outcomes in advanced NSCLC patients.

Effect of body mass index and cholesterol-rich apolipoprotein-B-containing lipoproteins on clinical outcome in NSCLC patients treated with immune checkpoint inhibitors-based therapy: A retrospective analysis.

Obesity and hypercholesterolemia are linked to unfavor clinical outcomes. Recent studies declared the paradox that high body mass index (BMI) and serum cholesterol were independently connected to better clinical outcome of immune checkpoint inhibitors (ICIs) monotherapy in non-small cell lung cancer (NSCLC). The aim of the study is to investigate the prognosis of BMI and serum cholesterol in ICIs-based therapy. This is a retrospective study of 95 NSCLC patients treated with ICIs-based therapy at the Department of Oncology and Lung Cancer Center of China-Japan Friendship Hospital. Treatment efficacy was assessed using durable clinical benefit (DCB) versus nondurable benefit (NDB), best response (active vs. nonactive), and progression-free survival (PFS). The prognostic value of BMI, LDL-C, and RC was determined by multivariate regression analyses, while controlling for confounding factors including age, gender, diabetes status, smoking history, and statin usage. BMI was considered a confounding factor in the analysis when examining the impact of lipoproteins. In our study, we found that in the whole group, BMI ≥25 kg/m2 was linked to a higher risk of poor therapeutic response (OR = 5.92, 95% CI 1.99-19.51, p.val = 0.002) and shorter progression-free survival (HR = 3.00, 95% CI 1.59-5.68, p.val = 0.001). In addition, low levels of RC were associated with better therapeutic response (OR = 0.12, 95% CI 0.02-0.64, p.val = 0.019), while low levels of serum LDL-C were found to predict longer PFS (HR = 0.40, 95% CI 0.19-0.82, p.val = 0.012). These associations were consistent in advanced NSCLC patients receiving ICIs and chemotherapy. Our study suggest that BMI ≥25 kg/m2 and elevated levels of apoB-containing lipoproteins, including LDL-C and RC, could potentially serve as useful prognostic markers for predicting poor treatment outcomes in advanced NSCLC patients treated with the combination of chemotherapy and ICIs.

Lipid alterations play a role in the integration of PD-1/PD-L1 inhibitors and anlotinib for the treatment of advanced non–small-cell lung cancer

BackgroundStudies have shown that integrating anlotinib with programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors enhances survival rates among progressive non–small-cell lung cancer (NSCLC) patients lacking driver mutations. However, not all individuals experience clinical benefits from this therapy. As a result, it is critical to investigate the factors that contribute to the inconsistent response of patients. Recent investigations have emphasized the importance of lipid metabolic reprogramming in the development and progression of NSCLC.MethodsThe objective of this investigation was to examine the correlation between lipid variations and observed treatment outcomes in advanced NSCLC patients who were administered PD-1/PD-L1 inhibitors alongside anlotinib. A cohort composed of 30 individuals diagnosed with advanced NSCLC without any driver mutations was divided into three distinct groups based on the clinical response to the combination treatment, namely, a group exhibiting partial responses, a group manifesting progressive disease, and a group demonstrating stable disease. The lipid composition of patients in these groups was assessed both before and after treatment.ResultsSignificant differences in lipid composition among the three groups were observed. Further analysis revealed 19 differential lipids, including 2 phosphatidylglycerols and 17 phosphoinositides.ConclusionThis preliminary study aimed to explore the specific impact of anlotinib in combination with PD-1/PD-L1 inhibitors on lipid metabolism in patients with advanced NSCLC. By investigating the effects of using both anlotinib and PD-1/PD-L1 inhibitors, this study enhances our understanding of lipid metabolism in lung cancer treatment. The findings from this research provide valuable insights into potential therapeutic approaches and the identification of new therapeutic biomarkers.

Clinical outcomes of advanced NSCLC patients with different EGFR exon 19 deletion subtypes treated with first-line tyrosine kinase inhibitors: A single-center ambispective cohort study.

Clinical significance of various subtypes of epidermal growth factor receptor (EGFR) exon 19 deletion (ex19del) mutation in non-small cell lung cancer (NSCLC) remains unclear. We analyzed EGFR ex19del subtypes in NSCLC patients receiving first-line tyrosine kinase inhibitor (TKI) therapy at our center (January 2018-June 2022) and correlated them with median progression-free survival (mPFS) and median overall survival (mOS). We identified 17 different EGFR ex19del variants in 101 patients. Between the classic (E746_A750del, 64.4%) and nonclassic groups (the rest variants), no significant difference was observed in mPFS (13.5 vs. 19.3 months, p = 0.18) or mOS (44.1 vs. 77.0 months, p = 0.06). mPFS showed no significant difference between ex19del subgroups classified based on the presence of insertion (ex19delins), starting position or length of deletion. However, patients with ex19delins starting at E746 showed longer mPFS than the others (29.7 vs. 12.5 months, p = 0.04), and patients with ex19del of 15 nucleotides had shorter mOS than the others (44.1 vs. 77.0 months, p = 0.03). In multivariate analysis, ex19delins independently predicted a better PFS (HR = 0.311, p = 0.03); however, 15 nucleotide deletion was no longer associated with OS (HR = 0.181, p = 0.11). Secondary T790M mutation incidence was significantly higher in the ex19del subgroup starting at E746 than the others (64.7% vs. 30.8%, p = 0.04). Our study revealed potential differences in TKI efficacy, resistance mechanism, and prognosis of various EGFR ex19del subtypes in NSCLC, underscoring the need for precise selection of first-line therapy.

Clinical outcomes of patients with advanced NSCLC with different EGFR exon 19 deletion subtypes treated with first-line tyrosine kinase inhibitors.

e21034 Background: Epidermal growth factor receptor (EGFR) exon 19 deletion (Ex19del) in non-small cell lung cancer (NSCLC) consists of many subtypes, and their sensitivity to tyrosine kinase inhibitors (TKIs) has not been clearly defined. This study aimed to investigate the clinical outcomes of advanced NSCLC patients with different EGFR ex19del subtypes treated with different TKIs. Methods: We retrospectively analyzed stage IIIB-IV NSCLC patients with EGFR Ex19del and first-line TKIs therapy. E746_A750del was defined as classic group, and the others as non-classic group, which was further divided into subgroups according to deletion with or without insertion, starting codon or length of deletion. The primary endpoint was progression free survival (PFS). Results: There were 17 Ex19del subtypes identified in 101 patients. The frequency of E746_A750del was 64.4% (65/101), and the top three frequent non-classic subtypes were L747_T751del (6.9%, 7/101), L747_P753delinsS (5.9%, 6/101) and E746_S752delinsV (5.0%, 5/101). In all patients, the median PFS (mPFS) of first-line TKIs in classic and non-classic groups were 14.3 months (m) and 19.3 m ( p &gt; 0.05). In non-classic group, the mPFS in deletion with insertion (delins) and without insertion subgroups were 25.3 m and 11.2 m; in deletion starting with E746 and with other codon subgroups were 29.7 m and 19.3 m; and in deletion length of 15 nucleotides (n) and of other length subgroups were 11.2 m and 25.3 m. The mPFS of these non-classic subgroups were not statistically different with that of classic group ( p &gt; 0.05). In all patients, the mPFS of first-line therapy with the 1st, 2nd and 3rd generation TKIs were 17.4 m, 15.6 m and 20.5 m, respectively ( p＞0.05); in classic group, the mPFS were 14.3 m, 16.9 m and 20.5 m, respectively ( p＞0.05). However, in non-classic delins subgroup (29.7 m, 15.6 m and 11.9 m) and in deletion length of ≥18 n subgroup (25.3 m，12.3 m and 11.9 m), the 1st generation TKIs had an insignificantly longest mPFS ( p＞0.05). When resistant to 1st or 2nd generation TKIs, patients in classic group showed a trend of higher incidence of T790M mutation than non-classic group (72.0% vs 43.8%, p = 0.070). In multivariant analysis, pleural metastasis (PM) had interaction with Ex19del grouping, warranting stratification analysis. In patients without PM, the mPFS of first-line TKIs in classic group was significantly shorter than non-classic group (13.8 m and 29.7 m, p = 0.026). However, in patients with PM, the mPFS of classic group was numerically longer than non-classic group (16.9 m and 11.7 m, p &gt; 0.05), with the shortest mPFS in non-classic without insertion subgroup, and in non-classic with 15 n deletion subgroup. Conclusions: In advanced NSCLC patients with EGFR Ex19del, the efficacy of first-line TKIs therapy was affected by the presence of pleural metastasis, Ex19del subtypes and different generation of TKIs.

Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) or combined with chemotherapy exhibit substantial efficacy for the treatment of advanced non-small cell lung cancer (NSCLC). However, reliable biomarkers that can monitor response to first-line ICIs ± chemotherapy remain unclear. A total of 16 tumor tissues and 46 matched peripheral blood samples at baseline and during treatment were retrospectively collected from 19 locally advanced or metastatic NSCLC patients. The circulating tumor DNA (ctDNA) burden by tumor-informed assay was detected to monitor and predict the therapeutic response and survival of NSCLC patients treated with first-line ICIs or plus chemotherapy. We found that ctDNA was only positively detected in one patient by tumor-agnostic assay with a mean variant allele fraction (VAF) of 6.40%, whereas it was positively detected in three patients by tumor-informed assay with a mean VAF of 8.83%, 0.154%, and 0.176%, respectively. Tumor-informed assays could sensitively detect ctDNA in 93.75% (15/16) of patients. Trends in the level of ctDNA from baseline to first evaluation was consistent with the radiographic changes. There was a greater decrease in ctDNA after treatment compared with baseline in patients with partial response compared to patients with stable disease/progressive disease. Patients with over a 50% reduction in ctDNA had a significant progression-free survival and overall survival benefit. The tumor-informed assay was favorable for ctDNA detection, and early dynamic changes in plasma ctDNA may be a valuable biomarker for monitoring the efficacy and predicting the outcome in advanced NSCLC patients treated with first-line ICIs ± chemotherapy.

Comparison of the prognosis of symptomatic cerebral infarction and pulmonary embolism in patients with advanced non-small cell lung cancer.

Lung cancer patients face a high risk of thromboembolism (TE), which is considered to be a poor prognostic factor. However, the impact of symptomatic cerebral infarction (CI) and pulmonary embolism (PE) on the prognosis of advanced non-small cell lung cancer (NSCLC) patients is not fully understood. We retrospectively identified 46 patients with advanced NSCLC who developed symptomatic CI or PE at five hospitals in Japan between January 2010 and December 2019. Prognosis and biomarker levels after incident CI and PE were investigated. Of the 46 patients, 36 developed symptomatic CI, and 10 developed symptomatic PE. The median follow-up duration after incident CI and PE was 18.2months. Although the proportion of Common Terminology Criteria for Adverse Events grade 4 tended to be higher in patients with PE than in those with CI (30% vs. 11%, p=0.16), the overall survival (OS) after incident TE tended to be worse in patients with CI than in those with PE (median 2.3months vs. 9.1 months, log-rank test p=0.17). Multivariate analysis showed that OS after CI was worse in patients with high D-dimer (DD) levels than in those with low DD levels at the time of incident CI (median 1.3months vs. 8.3 months, log-rank p < 0.001). This retrospective study demonstrated that the prognosis of patients tended to be poorer after CI than after PE. The DD levels at the time of incident CI might be a promising predictor of clinical outcomes in advanced NSCLC patients who develop CI.

Assessing Potential Factors Influencing the Efficacy of Immune Checkpoint Inhibitors with Radiation in Advanced Non-Small-Cell Lung Cancer Patients: A Systematic Review and Meta-Analysis.

Recent evidence suggests that combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) may result in better outcomes. In this study, we assessed the efficacy and safety of ICI plus radiation versus ICI alone and explored potential factors affecting its efficacy in advanced non-small-cell lung cancer (NSCLC) patients. The databases including PubMed and Embase were searched to retrieve eligible studies comparing the efficacy and safety outcomes in advanced NSCLC patients after ICIs ± RT treatments. We performed subgroup analyses to identify potential prognostic factors from radiation details and study types. The odds ratio (OR) of objective response rate (ORR) and disease control rate (DCR), hazard ratio (HR) of progression-free survival (PFS) and overall survival (OS), and risk ratio (RR) of adverse events were used to represent the outcome effects. 26 eligible studies with 14192 cases were included. The results showed that the ORR (OR = 0.63, 95% CI: 0.42, 0.93; p = 0.02) and DCR (OR = 0.55, 95% CI: 0.36, 0.82; p < 0.01) of RT + ICIs groups were significantly higher than those of the ICIs alone group. The median PFS and OS for ICIs versus RT + ICIs were 2.2 versus 4.4 months and 9.0 versus 13.4 months, respectively. Patients in the ICIs plus RT group had a significantly better PFS (HR = 0.72, 95% CI: 0.64, 0.81; p < 0.01) and OS (HR = 0.74, 95% CI: 0.65, 0.83; p < 0.01) when compared to those in the ICIs group. In terms of adverse events, the risk of pneumonia was not significantly increased in patients treated with both ICIs and RT when compared to ICIs group alone (risk ratio = 0.89; 95% CI: 0.55, 1.44; p = 0.63). The correlation analysis found that PFS was significantly correlated with OS (p = 0.02). The subgroup analysis results showed that significant improvements in OS were observed in non-palliative RT group (HR = 0.29, 95% CI: 0.13, 0.65; p < 0.01) and extracranial RT group (HR = 0.70, 95% CI: 0.59, 0.83; p < 0.01). RT type could also be a prognostic factor associated with the OS (for conventional RT: HR = 0.68 and p = 0.22; for stereotactic body radiation therapy: HR = 0.77 and p < 0.01). However, concerning RT timing, the results showed a similar trend in reducing mortality risk (for previous RT: HR = 0.64 and p = 0.21; for concurrent RT: HR = 0.35 and p = 0.16). RT plus ICIs is associated with improved survival for advanced NSCLC patients, especially for those with non-palliative RT. Further clinical trials are needed to validate its effect on survival outcomes.

SOCS3 protein expression predicts the responses of advanced non-small cell lung cancer patients to platinum-based chemotherapy.

This study sought to assess the relationship between suppressor of cytokine signaling 3 (SOCS3) expression, SOCS3 promoter methylation status, and platinum-based chemotherapy responses in advanced non-small cell lung cancer (NSCLC) patients. A total of 400 advanced NSCLC patients with inoperable disease were enrolled in this study. All the patients underwent platinum-based chemotherapy treatment, and the clinical and prognostic outcomes of these patients were analyzed. The SOCS3 protein expression and SOCS3 promoter methylation status of the tumor tissues in these patients were also tested by immunohistochemistry and polymerase chain reaction (PCR), respectively. In addition, we knocked down SOCS3 expression via small-interfering RNA (siRNA) in the lung cancer cell lines and conducted in vitro analyses to examine cell viability and apoptosis. Patients with higher expression levels of SOCS3 were found to have a lower average tumor stage, higher average tumor differentiation, and higher rates of positive chemotherapy responses than those with lower expression levels of SOCS3. SOCS3 promoter methylation was also found to be correlated with chemotherapy responses in these patients. In the prognostic analyses, only SOCS3 expression, but not SOCS3 promoter methylation, was found to be predictive of outcomes in advanced NSCLC patients. We also found that the pro-apoptotic effects of SOCS3 were mediated by the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways in the lung cancer cells. Currently, there is a lack of reliable biomarkers for predicting the responses of NSCLC patients to chemotherapy. Our results may aid in clinical evaluations of NSCLC patients.

339P Analysis of first- and second-line immunotherapy efficacy in metastatic non-small cell lung cancer with low PD-L1 expression

Immune checkpoint inhibitors (ICI) improve overall survival (OS) in non-small cell lung cancer (NSCLC) but the efficacy of first- vs second-line ICI is unknown. We compared the outcomes of advanced NSCLC patients with <50% PD-L1 expression who received first- and second-line ICI.

Positive Correlation of Peripheral CD8+ T Lymphocytes with Immune-Related Adverse Events and Combinational Prognostic Value in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

Simple SummaryImmune checkpoint inhibitors are widely used in clinical practice and have demonstrated remarkable efficacy in advanced non-small cell lung cancer (NSCLC). However, their use is also commonly accompanied by immune-related adverse events (irAEs), and markers that are able to predict the onset of irAEs represent an urgent need. In this study, we found that the baseline level of peripheral CD8+ T lymphocytes was the independent risk factor of the onset of irAEs, and it was associated with longer survival in advanced NSCLC patients treated with PD-1/PD-L1 inhibitors. Furthermore, the study showed the combinational predictive value of baseline CD8+ T lymphocytes and the onset of irAEs for the clinical outcomes.Immune checkpoint inhibitors (ICIs) therapy has revolutionized the treatment patterns of non-small cell lung cancer (NSCLC). However, patients treated with ICIs may experience immune-related adverse events (irAEs). Markers that could predict the onset of irAEs are still unclear. Here, we report the possible correlation of baseline peripheral lymphocytes with irAEs and clinical outcomes in advanced NSCLC patients receiving ICIs. A total of 109 advanced NSCLC patients treated with ICIs from April 2017 to January 2021 were analyzed retrospectively. Logistic and Cox regression analyses was applied to evaluate independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). Among these patients, 55 (50.5%) patients experienced irAEs. The level of CD8+ T lymphocytes at baseline was the independent risk factor for the onset of irAEs (p = 0.008). A higher level of CD8+ T lymphocytes was associated with longer PFS (11.0 months vs. 3.0 months, p < 0.001) and OS (27.9 months vs. 11.7 months, p = 0.014). Furthermore, patients who had higher baseline CD8+ T lymphocytes and experienced irAEs had a longer PFS (18.4 months vs. 2.2 months, p < 0.001) and OS (32.8 months vs. 9.0 months, p = 0.001) than those who had lower CD8+ T lymphocytes and no irAEs. Our study highlights the value of baseline peripheral CD8+ T lymphocytes as a predictive factor for irAEs in advanced NSCLC patients receiving ICIs. In addition, patients who have higher baseline CD8+ T lymphocytes and experience irAEs would have a superior PFS and OS.

Sex-Based Clinical Outcome in Advanced NSCLC Patients Undergoing PD-1/PD-L1 Inhibitor Therapy-A Retrospective Bi-Centric Cohort Study.

Simple SummaryRetrospective analyses suggest that men treated with immune-checkpoint inhibitor (ICI) monotherapy for non-small cell lung cancer (NSCLC) have better outcomes than women. However, female patients have more favorable responses when chemotherapy (CHT) is given together with ICI. We aimed to explore the clinical impact of such sex differences in two cohorts, receiving ICI monotherapy or ICI-CHT combination, respectively. We found no significant difference in outcomes between men and women treated with either therapeutic regimen. However, known predictive factors for ICI response such as the expression of programmed-death ligand 1 (PD-L1) on tumor cells or patient performance status had significant implications for men rather than for women. Our results warrant increased research efforts to clarify sex-specific differences in anti-tumor immune response mechanisms and in the efficacy of ICI therapies, especially in women. Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy (n = 228) or ICI-CHT combination treatment (n = 80) for advanced NSCLC. Kaplan–Meier analyses were used to calculate progression-free (PFS) and overall survival (OS), influencing variables were evaluated using Cox-regression analyses. No significant sex differences for PFS/OS could be detected in either cohort. Men receiving ICI monotherapy had a statistically significant independent impact on PFS by Eastern Cooperative Oncology Group performance status (ECOG) ≥2 (hazard ratio (HR) 1.90, 95% confidence interval (CI): 1.10–3.29, p = 0.021), higher C-reactive protein (CRP; HR 1.06, 95%CI: 1.00–1.11, p = 0.037) and negative programmed death-ligand 1 (PD-L1) status (HR 2.04, 95%CI: 1.32–3.15, p = 0.001), and on OS by CRP (HR 1.09, 95%CI: 1.03–1.14, p = 0.002). In men on ICI-CHT combinations, multivariate analyses (MVA) revealed squamous histology (HR 4.00, 95%CI: 1.41–11.2, p = 0.009) significant for PFS; and ECOG ≥ 2 (HR 5.58, 95%CI: 1.88–16.5, p = 0.002) and CRP (HR 1.19, 95%CI: 1.06–1.32, p = 0.002) for OS. Among women undergoing ICI monotherapy, no variable proved significant for PFS, while ECOG ≥ 2 had a significant interaction with OS (HR 1.90, 95%CI 1.04–3.46, p = 0.037). Women treated with ICI-CHT had significant MVA findings for CRP with both PFS (HR 1.09, 95%CI: 1.02–1.16, p = 0.007) and OS (HR 1.11, 95%CI: 1.03–1.19, p = 0.004). Although men and women responded similarly to both ICI mono- and ICI-CHT treatment, predictors of response differed by sex.

MA17.01 Reduced FEV1 as Prognostic Factors in Patients With Advanced NSCLC Receiving Immune Checkpoint Inhibitors

The impact of reduced pulmonary function on patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI) is not fully elucidated. The aim of study is to investigate the influence of pulmonary function on the prognosis and treatment outcome in advanced NSCLC patients receiving ICI. Data were collected retrospectively from 151 patients with stage IV NSCLC who received ICI and completed spirometry before ICI therapy in Taipei Veterans General Hospital between January 2016 and December 2020. The co-primary end points were overall survival (OS) and progression-free survival (PFS) between groups divided by 80% predicted FEV1 since ICI therapy started; the secondary outcomes were objective response rate. Among 151 patients enrolled to this study, 67.5% of patients were men, 75.5% were adenocarcinoma, 24.5% had known targetable driver mutation, 33.8% received first-line ICI, and 62.8% received ICI monotherapy. The objective response rate was 24.5% and disease control rate was 54.3%. In multivariable analysis, patient with reduced FEV1 had inferior PFS (50%≤ FEV1< 80% vs. FEV1≥80%, adjusted HR= 1.67; 30%≤ FEV1< 50% vs. FEV1≥80%, adjusted HR= 1.822, FEV1< 30% vs. FEV1≥ 80%, adjusted HR= 10.39, P=0.003), and OS (50%≤ FEV1<80% vs. FEV1≥ 80%, adjusted HR= 2.10; 30%≤ FEV1< 50% vs. FEV1≥ 80%, adjusted HR= 3.43; FEV1< 30% vs. FEV1≥ 80%, adjusted HR= 14.41, P<0.001). Median PFS and OS in the preserved FEV1 group (≥80% predicted FEV1) compared to the reduced FEV1 group (<80% predicted FEV1) were 5.4 vs. 2.9 months (adjusted HR= 1.80, P=0.006) and 34.9 vs. 11.1 months (adjusted HR=2.50, P<0.001), respectively. The other independent prognostic factors of OS include stage IVA disease (adjusted HR= 0.56, P=0.032), initial liver metastasis (adjusted HR= 2.15, P=0.030), and ICI monotherapy. (adjusted HR= 1.73, P=0.042)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Reduced FEV1 is strongly associated with inferior clinical outcomes in patients with advanced NSCLC treated with ICI.

P16.06 Comparison of Clinical Outcomes of Patients With Advanced NSCLC In Clinical Trials and in the Real World Received PD-1/PD-L1 Inhibitor

Although PD-1/PD-L1 inhibitors have become the standard treatment for patients with advanced non-small cell lung cancer (NSCLC), data from clinical trials are difficult to be verified in the real world. This study aims to compare the differences in population characteristics, treatment modes and clinical outcomes of advanced NSCLC patients received PD-1/PD-L1 inhibitors between the real-world (RWS) and the clinical study (RCT).

MA09.03 Peripheral CD8+ T Cells Predicts Immune-Related Adverse Events and Survival in Advanced Non-Small Cell Lung Cancer Treated With Immunotherapy

Immune checkpoint inhibitors, which have been approved for the treatment of non-small cell lung cancer (NSCLC), often cause unique side effects, named immune-related adverse events (irAEs). Peripheral blood biomarkers have shown a great potential as predictors of clinical outcomes and irAEs due to minimal invasiveness and convenience. This study aims to determine the association between baseline subsets of lymphocytes and irAEs and clinical outcomes in advanced NSCLC patients after immune checkpoint inhibitors therapy.

Analysis of the Gut Microbiota: An Emerging Source of Biomarkers for Immune Checkpoint Blockade Therapy in Non-Small Cell Lung Cancer.

Simple SummaryThe immune checkpoint blockade (ICB), and concretely the blockade of the PD1/PDL1 axis, has opened up a new standard of treatment for non-small cell lung cancer (NSCLC). However, despite substantial advances in clinical care, many patients still remain refractory to these therapies. Biomarkers such as PD-L1 expression and tumor mutational burden have been associated with ICB efficacy, but the mechanisms underlying variable responses are not yet fully understood. Recently, the differential composition of the gut microbiota was studied as one of the variables accounting for interpatient heterogeneity in ICB responses. To better understand the potential role of the gut microbiota as a biomarker for immunotherapy, we prospectively collected microbiota samples from advanced NSCLC patients starting treatment with ICB. The identification of certain bacteria genera associated with clinical outcomes to ICB in NSCLC may provide novel potential predictive and prognostic biomarkers useful for patient selection and therapy optimization.Background: The human gut harbors around 1013–1014 microorganisms, collectively referred to as gut microbiota. Recent studies have found that the gut microbiota may have an impact on the interaction between immune regulation and anti-cancer immunotherapies. Methods: In order to characterize the diversity and composition of commensal microbiota and its relationship with response to immune checkpoint blockade (ICB), 16S ribosomal DNA (rDNA) sequencing was performed on 69 stool samples from advanced non-small cell lung cancer (NSCLC) patients prior to treatment with ICB. Results: The use of antibiotics and ICB-related skin toxicity were significantly associated with reduced gut microbiota diversity. However, antibiotics (ATB) usage was not related to low ICB efficacy. Phascolarctobacterium was enriched in patients with clinical benefit and correlated with prolonged progression-free survival, whereas Dialister was more represented in patients with progressive disease, and its higher relative abundance was associated with reduced progression-free survival and overall survival, with independent prognostic value in multivariate analysis. Conclusions: Our results corroborate the relation between the baseline gut microbiota composition and ICB clinical outcomes in advanced NSCLC patients, and provide novel potential predictive and prognostic biomarkers for immunotherapy in NSCLC.

Comparison of population characteristics, treatment modes, and clinical outcomes of patients with advanced non-small cell lung cancer in clinical trials and in the real world received PD-1/PD-L1 inhibitor.

e18733 Background: Although PD-1/PD-L1 inhibitors have become the standard treatment for patients with advanced non-small cell lung cancer (NSCLC), data from clinical trials are difficult to be verified in the real world. This study aims to compare the differences in population characteristics, treatment modes and clinical outcomes of advanced NSCLC patients received PD-1/PD-L1 inhibitors between the real-world (RWS) and the clinical study (RCT). Methods: This study enrolled 305 advanced NSCLC patients who received at least one PD-1/PD-L1 inhibitor treatment selected in the Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital Information System and the Zero Krypton database during January 2016 to September 2019. The patients were divided into RWS group and RCT group. The PD-1/PD-L1 inhibitors included pembrolizumab, sintilizumab, nivolizumab, tislelizumab, carrelizumab, teriprizumab, durvalizumab and Atezolizumab. We performed paired analysis in clinical characteristics and treatment modes. Results: There were 155 cases in the RCT group and 150 cases in the RWS group. The RCT group consisted of higher proportion in male (79.4%) and squamous-carcinoma type (41.3%) than the RWS group, while more patients of brain metastasis (28%) and combination therapy (50.7%) in the RWS group. The ORRs were 42.4% and 20.6% respectively in the RCT and RWS groups receiving first-line treatment with PD-1/PD-L1 inhibitors, and the difference was statistically different. Moreover, the ORRs were 42.4% and 20.6% respectively in the RCT and RWS groups receiving PD-1/PD-L1 inhibitor as second-line treatment, without statistical difference. The progression-free survival (PFS) was 15.5 vs. 13.5 months in the RCT and RWS groups ( P= 0.91), and the median overall survival (OS) was 25.4 vs. 33.8 months respectively ( P= 0.24), with no statistical difference. After propensity match of baseline characteristics of the two groups of patients, it contained 108 patients in the RCT and RWS groups. The PFS was 13.3 vs. 13.3 months in the RCT and RWS groups ( P= 0.47), and the median OS was 21.1 vs. 23.2 months ( P= 0.58), with no statistical difference. Conclusions: Although more female, brain metastases and adenocarcinoma patients receiving PD-1/PD-L1 inhibitors in the real world, the clinical benefits were consistent with those in clinical trials. The results of propensity matching on the baseline characteristics of patients supported this conclusion.

Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors: A real-world perspective.

e21213 Background: Lung cancer is the leading cause of death in males and females in the United States. Approximately 85% of all cases are classified as non-small cell lung cancer (NSCLC) with majority diagnosed at an advanced stage. Unfortunately, response to traditional chemotherapy (ChT) has been poor with a five-year survival rate of 6% in metastatic NSCLC. Immune checkpoint inhibitors (ICI) have changed the therapeutic landscape for advanced NSCLC and are being utilized alone or in combination with ChT as the standard first-line therapy. With widespread use of ICIs, immune-related adverse events (irAE) are commonly seen and in some studies their occurrence correlates with improved outcomes. The aim of our study was to evaluate whether development of irAEs has an impact on survival in NSCLC. Methods: We performed a retrospective analysis on stage IV NSCLC patients treated with ChT, ChT plus ICI, or ICI monotherapy from December 2016 to December 2019. Univariable and multivariable analyses identified characteristics predictive of progression-free survival (PFS) and overall survival (OS). OS was calculated using Kaplan Meier curves. Log-rank statistics were used to assess statistical significance between groups. Multivariable logistic regression was performed to identify predictors of survival. Results: 193 patients were evaluated out of which 92 (47.2%) received ChT plus pembrolizumab, 69 (35.4%) received pembrolizumab alone and 32 (16.4%) received ChT alone. 130 patients were found to have no irAEs compared to 57 patients who were noted to have any grade of irAE. The median PFS was 17.4 months (irAE group) vs. 8.5 months (non-irAE group) with hazard ratio (HR) of 0.58 (95% CI: 0.41 to 0.80, p = 0.001). The median OS was 29.4 months (irAE group) vs. 14.4 months (non-irAE group) with HR of 0.56 (95% CI: 0.39 to 0.82, p = 0.0026). A multivariate analysis was performed for age, gender, ECOG performance status, insurance status, BMI, PDL1 status and smoking history, amongst other variables. Worse survival outcomes were noted with an ECOG performance status ≥ 2, no history of smoking, and involvement of palliative care. Multivariable logistic regression analysis showed that PDL-1 expression &gt; 50% was the only predictor of developing an irAE. Of note, receipt of ChT in combination with pembrolizumab compared to pembrolizumab alone did not predict for development of irAE. Conclusions: Development of irAEs was associated with doubling of PFS and OS, regardless of whether the ICI was administered alone or in combination with ChT. The differences were statistically significant regardless of age, gender, race, BMI, insurance status or performance status. Our study highlights the correlation between development of irAEs and improved survival outcomes in advanced NSCLC patients treated with ICIs.

Tumor burden as possible biomarker of outcome in advanced NSCLC patients treated with immunotherapy: a single center, retrospective, real-world analysis.

Aim:The role of tumor burden (TB) for patients with non-small cell lung cancer (NSCLC) receiving immunotherapy is still unknown. The aim of this analysis was to analyze the prognostic value of TB in a real-world sample of advanced NSCLC patients.Methods:Sixty-five consecutive patients with advanced NSCLC treated with immunotherapy as first or second line therapy were retrospectively analyzed between August 2015 and February 2018. TB was recorded at baseline considering sites and number of metastases, thoracic vs. extrathoracic disease, measurable disease (MD) vs. not-MD (NMD) and evaluating dimensional aspects as maximum lesion diameter (cut-off = 6.3 cm), sum of the 5 major lesions diameters (cut-off = 14.3 cm), and number of sites of metastases (cut-off > 4). All cut-offs were calculated by receiver operating characteristic curves. Median overall survival (OS) was estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses.Results:Median age was 70 years and most patients (86.2%) had a good performance status (PS-Eastern Cooperative Oncology Group < 2). No significant difference in OS was noted between subgroups of patients according to TB. Bone metastases (BM) had a negative prognostic impact [median OS (mOS), 13.8 vs. 70.0 months, P = 0.0009; median progression free survival in the second line (mPFS2) 2.97 vs. 8.63 months; P = 0.0037]. Patients with NMD had a poorer prognosis (mOS, 15.9 months vs. not reached, P < 0.0001; mPFS2 3.8 vs. 12.2 months; P = 0.0199). Patients with disease limited to the thorax had a better prognosis compared to patients with involvement of extrathoracic sites (mOS, 70 vs. 17.3 months; P = 0.0136). Having more than 4 metastatic sites resulted as a negative prognostic factor (mOS, 15.9 vs. 25.2 months; P = 0.0106). At multivariate analysis, BM, NMD, extrathoracic disease and number of sites of metastases > 4 were negative prognostic factors (P < 0.0001).Conclusions:This study underlines the negative prognostic impact of specific metastatic sites, presence of NMD and extrathoracic disease in advanced NSCLC patients treated with immunotherapy. However, TB does not appear to affect the outcome of these patients.