Advanced Non-small Cell Lung Cancer Research Articles

Characterization of renal injury in non-squamous non-small cell lung cancer patients treated with pemetrexed: A single-center retrospective study.

Pemetrexed is a key therapeutic agent for advanced non-squamous non-small cell lung cancer (Nsq-NSCLC), yet it is associated with renal toxicity. This study aims to elucidate the incidence, risk factors, and survival impact of renal injury in patients with Nsq-NSCLC treated with pemetrexed. We conducted a retrospective study including 136 patients with Nsq-NSCLC treated with pemetrexed. Data on demographics, renal function, progression-free survival (PFS), and overall survival (OS) were collected. Renal injury was defined as a reduction above 25% in estimated glomerular filtration rate (eGFR) from baseline. Its associated risk factors were analyzed using logistic regression, and impact on survival was analyzed using log-rank test. The creatinine clearance rate (CCr) was calculated, and a CCr < 45 mL/min served as a contraindication for continuing pemetrexed. The study found a 31.6% (43/136) incidence of renal injury, with 9.6% (13/136) having CCr < 45 mL/min and discontinuing pemetrexed. Univariate and multivariate analyses identified factors significantly associated with increased renal injury risk including older age, use of cisplatin, and higher number of pemetrexed cycles. The patients with renal injury had a median PFS (mPFS) of 13.5 months and a median OS (mOS) of 36.0 months, while the patients without had an mPFS of 9.0 months and an mOS of 35.0 months, and these differences were not statistically significant. Renal injury is a considerable complication in patients with Nsq-NSCLC undergoing pemetrexed treatment, with age, platinum type, and pemetrexed treatment cycles as key risk factors. These findings highlight the necessity for careful renal monitoring in this patient population.

Clinical characteristics and prognostic factors of epidermal growth factor receptor-mutated non-small cell lung cancer transformed into small-cell lung cancer after treatment

Objective: To analyze the clinical characteristics and prognostic factors of non-small cell lung cancer (NSCLC) patients with sensitive epidermal growth factor receptor (EGFR) mutations who developed small cell lung cancer (SCLC) transformation after treatment with EGFR tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective collection of clinical data for 21 patients with advanced EGFR mutant NSCLC who developed SCLC transformation after EGFR-TKI treatment at Beijing Chest Hospital, Capital Medical University from January 2015 to December 2021. The clinical characteristics were summarized and the prognosis analysis was conducted. Patients were followed up until February 2024. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in survival time (OS) between limited stage and extensive stage in transformed SCLC patients. Cox proportional hazards model was used to analyze the influencing factors of survival after SCLC transformation. Results: Among the 21 patients, there were 5 males and 16 females, with an age range of 33-74 years old [(58.9±2.6) years old]. All 21 patients were adenocarcinoma with sensitive EGFR mutations. There were 18 cases (85.7%) with EGFR gene 19del mutation, including 1 case of 19del+anaplastic lymphoma kinase (ALK) mutation, and 3 cases of L858R mutation. Among the transformed SCLC, there were 11 cases of pure SCLC and 10 cases of mixed SCLC (coexisting of adenocarcinoma and small cell carcinoma components). The median time from diagnosis of NSCLC to SCLC transformation was 12.0 months (95%CI: 7.6-16.3 months). Among the 21 cases of SCLC transformation, there were 13 cases with the extensive stage and 8 cases with the limited stage. Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS. Five cases had partial remission, 5 cases were stable, 3 cases had disease progression, and 3 cases cloud not be evaluated. The median progression free survival time (PFS) was 4.8 months (95%CI: 2.8-6.8 months). The median survival time (OS) after SCLC transformation in 21 patients was 10.6 months (95%CI: 7.0-14.2 months), with a median OS of 8.8 months (95%CI: 6.3-11.4 months) for patients with the extensive stage and 27.5 months (95%CI: 9.6-34.4 months) for patients with the limited stage, with statistically significant differences (P=0.002). Cox proportional hazards model analysis showed that the limited stage after SCLC transformation was a protective factor for OS (HR=0.32, 95%CI: 0.12-0.73, P=0.010). The median OS of 21 patients from the diagnosis of lung cancer was 24.9 months (95%CI: 13.0-36.7 months). Conclusions: NSCLC patients with SCLC transformation are all adenocarcinomas, and the proportion of EGFR19del mutations is relatively high. After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.

Perspectives on Drug Product Design Among Patients with Lung Cancer in the United Kingdom.

The use of oral anticancer medications has become more prevalent in cancer therapy. This is particularly the case in the management of advanced non-small cell lung cancer (NSCLC). However, when the treatment delivery interaction between the patient and the healthcare provider is removed, the risk of non-adherence increases. Insights into patient preferences can allow drug product formulation scientists to design more patient-centric medications that may promote an increase in adherence which, in turn, may lead to more beneficial health outcomes. We conducted an advisory board with patients with NSCLC in the United Kingdom to elicit and understand preferences for drug product attributes related to appearance, instructions, and modality. The advisory board was preceded by a quantitative preference survey that included three object-case best-worst scaling exercises and was followed by administering the same survey to a broader group of patients to confirm the results. Patients strongly prefer once-daily dosing over more frequent dosing, regardless of the number of pills because taking tablets or capsules multiple times each day can disrupt daily activities. In addition, patients place high importance on surface smoothness because a rough surface implies decreased swallowability. Finally, food restrictions involving directions regarding taking medication with or without food represent difficulties for patients with cancer. Results of the follow-up survey confirmed these results. Drug developers should attempt to limit the dosing of these medications to once-daily regimens, avoid surface roughness, and develop formulations that can be taken without regard to the timing of meals to the greatest extent possible.

Phase 1 Study of ROR1 Specific CAR T Cells in Advanced Hematopoietic and Epithelial Malignancies.

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is expressed in hematopoietic and epithelial cancers but has limited expression on normal adult tissues. This phase 1 study evaluated the safety of targeting ROR1 with autologous T-lymphocytes engineered to express a ROR1 chimeric antigen receptor (CAR). Secondary objectives evaluated persistence, trafficking, and antitumor activity of CAR T cells. Twenty-one patients with ROR1+ tumors received CAR T cells at one of four dose levels (DL): 3.3x105/1x106/3.3x106/1x107 cells/kg, administered after lymphodepletion with Cyclophosphamide/Fludarabine (Cy/Flu) or Oxaliplatin/Cyclophosphamide (Ox/Cy). Cohort A included patients with chronic lymphocytic leukemia (CLL, n=3); cohort B included patients with triple-negative breast cancer (TNBC, n=10) or non-small-cell lung cancer (NSCLC, n=8). A second infusion was administered to one patient in cohort A with residual CLL in the marrow and three patients in cohort B with stable disease after first infusion. Treatment was well tolerated apart from one dose limiting toxicity at DL4 in a patient with advanced NSCLC. Two of the three (67%) CLL patients showed robust CAR T expansion and a rapid antitumor response. In patients with NSCLC and TNBC, CAR T cells expanded to variable levels, infiltrated tumor poorly, and one of eighteen patients (5.5%) achieved partial response by RECIST 1.1. ROR1 CAR T cells were well tolerated in most patients. Antitumor activity was observed in CLL but was limited in TNBC and NSCLC. Immunogenicity of the CAR and lack of sustained tumor infiltration were identified as limitations.

Transpulmonary chemoembolization and microwave ablation for recurrent or advanced non-small cell Lung Cancer

To verify the treatment effect of the combination of transpulmonary chemoembolization (TPCE) and microwave ablation (MWA), targeting the treatment of recurrent or advanced non-small cell lung cancer (NSCLC). A total of 53 patients were studied and grouped according to the diameter of the largest pulmonary nodule, defined as index tumor size (ITS). Patients with an ITS > 3 cm (n = 20) were treated with TPCE and MWA. Patients with an ITS ≤ 3 cm were treated either with a combination therapy (n = 24) or MWA alone (n = 9). The treatment response, including complications and survival outcome, was then analyzed. After TPCE, there was an average ITS reduction of 0.91 cm, and 25% of patients in ITS > 3 cm were downgraded to ITS ≤ 3 cm. After TPCE, there were 12 patients (27%) with PR status and 32 (73%) with SD status. No PD patient in our case series was noted before MWA.The complication rate of MWA was significantly higher in ITS ≤ 3 cm than in ITS > 3 cm (p = 0.013). The median survival time (MST) was 26.7 months, and the time to progression was 13.2 months. The patients in the ITS ≤ 3 cm had longer MST than the others (31.6 vs. 15.8 months, p = 0.003). The significant prognostic factor was ITS > 3 cm (HR: 1.18, p = 0.02). A combination of TPCE and MWA might be feasible to control non-operable, recurrent, or advanced NSCLC.

Deep learning analysis of histopathological images predicts immunotherapy prognosis and reveals tumour microenvironment features in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer mortality worldwide. Immune checkpoint inhibitors (ICIs) have emerged as a crucial treatment option for patients with advanced NSCLC. However, only a subset of patients experience clinical benefit from ICIs. Therefore, identifying biomarkers that can predict response to ICIs is imperative for optimising patient selection. Hematoxylin and eosin (H&E) images of NSCLC patients were obtained from the local cohort (n = 106) and The Cancer Genome Atlas (TCGA) (n = 899). We developed an ICI-related pathological prognostic signature (ir-PPS) based on H&E stained histopathology images to predict prognosis in NSCLC patients treated with ICIs using deep learning. To accomplish this, we employed a modified ResNet model (ResNet18-PG), a widely-used deep learning architecture well-known for its effectiveness in handling complex image recognition tasks. Our modifications include a progressive growing strategy to improve the stability of model training and the use of the AdamW optimiser, which enhances the optimisation process by adjusting the learning rate based on training dynamics. The deep learning model, ResNet18-PG, achieved an area under the receiver operating characteristic curve (AUC) of 0.918 and a recall of 0.995 on the local cohort. The ir-PPS effectively risk-stratified NSCLC patients. Patients in the low-risk group (n = 40) had significantly improved progression-free survival (PFS) after ICI treatment compared to those in the high-risk group (n = 66, log-rank P = 0.004, hazard ratio (HR) = 3.65, 95%CI: 1.75-7.60). The ir-PPS demonstrated good discriminatory power for predicting 6-month PFS (AUC = 0.750), 12-month PFS (AUC = 0.677), and 18-month PFS (AUC = 0.662). The low-risk group exhibited increased expression of immune checkpoint molecules, cytotoxicity-related genes, an elevated abundance of tumour-infiltrating lymphocytes, and enhanced activity in immune stimulatory pathways. The ir-PPS signature derived from H&E images using deep learning could predict ICIs prognosis in NSCLC patients. The ir-PPS provides a novel imaging biomarker that may help select optimal candidates for ICIs therapy in NSCLC.

Novel Immunotherapeutics for the Treatment of Non-Small Cell Lung Cancer (NSCLC) Resistant to PD-1/PD-L1 Inhibitors.

Immunotherapy with PD-1/PD-L1 inhibitors is the standard method of care for the treatment of newly diagnosed advanced or metastatic NSCLC, with or without chemotherapy. Many tumors, however, develop resistance to these immunotherapy agents. There is a need to develop more effective therapies for patients with metastatic NSCLC in the second-line setting and beyond. In this review, we present an overview of novel immunotherapies being investigated regarding the treatment of these patients. We summarize completed, as well as ongoing, trials investigating these therapies as monotherapy or in combination with PD-1/PD-L1 inhibitors. These include immune co-stimulatory antibodies, T-cell agonists, oncolytic viruses, vaccines, TIL therapies, and CAR-T therapies.

18F]F-AraG Uptake in Vertebral Bone Marrow May Predict Survival in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-(L)1 Immunotherapy.

Despite the systemic impact of both cancer and the associated immune response, immuno-PET is predominantly centered on assessment of the immune milieu within the tumor microenvironment. The aim of this study was to assess the value of [18F]F-AraG PET imaging as a noninvasive method for evaluation of system-wide immune status of patients with non-small cell lung cancer before starting immunotherapy. Methods: Eleven patients with advanced non-small cell lung cancer were imaged with [18F]F-AraG before starting immunotherapy. Diagnostic [18F]FDG PET/CT scans were analyzed to assess differences in the extent of disease among patients. SUVmax, SUVmean, and total SUV (SUVtotal) from all tumor lesions, active lymph nodes, spleen, vertebral bone marrow, liver, thyroid, heart, and bowel were extracted from the baseline [18F]F-AraG scans, and discriminant and Kaplan-Meier analyses were performed to test their ability to predict patient response and overall survival. Results: The extent of the disease was variable in the patient cohort, but none of the [18F]FDG biomarkers associated with tumor burden (SUVmax, total metabolic tumor volume, and total lesion glycolysis) was predictive of patient survival. The differences in the [18F]F-AraG and [18F]FDG distribution were observed both within and between lesions, confirming that they capture distinct aspects of the tumor microenvironment. Of the 3 SUV parameters studied, [18F]F-AraG SUVtotal provided a dynamic range suitable for stratifying tumors or patients according to their immune activity. [18F]F-AraG SUVtotal measured in the lumbar and sacral vertebrae differentiated between patients who progressed on therapy and those who did not with 90.9% and 81.8% accuracy, respectively. The Kaplan-Meier analysis revealed that patients with high [18F]F-AraG SUVtotal in the lumbar bone marrow had significantly lower probability of survival than those with a low signal (P = 0.0003). Conclusion: This study highlights the significance of assessing systemic immunity and indicates the potential of the [18F]F-AraG bone marrow signal as a predictive imaging biomarker for patient stratification and treatment guidance.

Optimizing Treatment Strategies for Egfr-Mutated Non-Small-Cell Lung Cancer Treated with Osimertinib: Real-World Outcomes and Insights.

Background: Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), demonstrated superior efficacy over first-generation TKIs in the FLAURA trial, resulting in its approval as first-line therapy for metastatic non-small-cell lung cancer (NSCLC). However, the real-world application of these trial results requires an evaluation of sequential therapeutic strategies. Methods: This retrospective, non-interventional study utilized data from the Epidemiological Strategy and Medical Economics (ESME) platform, which includes information on patients treated for lung cancer since 2015. Out of 39,974 patients in the database, 624 patients with EGFR-mutant advanced NSCLC treated with osimertinib as first-line (L1, n = 198) or second-line (L2, n = 426) treatment after first- or second-generation TKIs (n = 1262) were identified. Patient demographics, disease characteristics, treatment strategies, and disease progression were examined. Survival analyses were performed using Kaplan-Meier estimates and Cox proportional-hazards models. Results: In the study population (n = 624), 73.4% were female, with a median age of 70 years (range 28-93). Brain metastases at the start of osimertinib treatment were observed in 282 patients. ECOG PS-2 was reported in 29.4% of patients. The T790M mutation in exon 20 was identified in 257/426 patients (60.3%) receiving osimertinib in L2. Median progression-free survival (PFS) was 12.4 months (95% CI [10.7-14.7]) for L1 and 7.4 months (95% CI [6.2-8.7]) for L2. Median overall survival (OS) from advanced diagnosis was 28.5 months (95% CI [26.3-38.7]) for osimertinib L1 and 29.9 months (95% CI [28.6-31.8]) for osimertinib L2 (HR = 0.93; 95% CI [0.75-1.16]; p = 0.50). For L1, median OS was 27.1 months (95% CI [22.0-30.2]) for patients with cerebral metastases and 38.7 months (95% CI [26.3-52.8]) for those without (HR = 0.73; 95% CI [0.48-1.11]; p = 0.15). Discussion: Patients in the real-world ESME database exhibited a poorer prognosis compared to those in the FLAURA trial. The presence of cerebral metastases at diagnosis worsens the prognosis.

Metabolic tumor volume assessed by 18F FDG - PET CT scan as a predictive biomarker for immune checkpoint blockers in advanced NSCLC and its biological correlates.

This study aimed to explore metabolic tumor volume (tMTV) as assessed 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT), and understand its biological meaning in patients with NSCLC exposed to immune checkpoint blockers(ICBs). In this study, patients with advanced NSCLC and a positive PET scan within 42 days of first line treatment were enrolled in 11 institutions across 4 countries. Total MTV (tMTV) was analyzed, with a 42% SUVmax threshold. Survival was analyzed according to high tMTV (≥ median). Plasma proteomic profile, whole exome, transcriptome and other analysis were performed on monocentric cohorts to explore its biological correlates. Of the 518 patients included, 167 received ICBs, 257 had chemotherapy plus ICBs, and 94 had chemotherapy. Median tMTV was 99 cm3. Median overall survival (OS) for patients with high tMTV treated with ICBs was 11.4 months vs 29.6 months (P<0.0012) for those with low tMTV. In patients receiving chemotherapy-ICB tMTV did not correlate with OS (P=0.099). In patients with PD-L1≥1% and high tMTV, chemotherapy-ICB combination was associated with longer OS compared with ICBs alone (20 vs 11.4 months,p=0.026), while no survival differences observed in low tMTV group. High tMTV correlated (and its detrimental effect seems to be driven by) a specific proteomic profile and increase in genomic instability. Our analysis indicates high tTMV is linked to an increase in systemic inflammation, specific cytokines production and chromosomal instability. tTMV may serve as one of the biomarker to select the best upfront strategy in patients with PD-L1 positive advanced NSCLC.

Body composition derangements in lung cancer patients treated with first-line pembrolizumab: A multicentre observational study.

While immune checkpoint inhibitors (ICIs) are increasingly reshaping the therapeutic landscape of non-small-cell lung cancer (NSCLC), only a limited proportion of patients achieve a relevant and long-lasting benefit with these treatments, calling for the identification of clinical and, ideally modifiable, predictors of efficacy. Body composition phenotypes may reflect aspects of patients' immunology and thereby their ability to respond to ICIs. This study aims to explore the possible association between pre-treatment body composition phenotypes, tumour response, and clinical outcomes in patients receiving first-line pembrolizumab monotherapy for advanced NSCLC. A retrospective review of consecutive patients with treatment-naïve NSCLC and PD-L1 expression ≥50% undergoing pembrolizumab at three academic institutions was performed. Pre-treatment body composition parameters were measured at the third lumbar vertebra level by computed tomography, defined using pre-established cut-offs. Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival and overall survival (PFS and OS), compared through the log-rank test and the Cox proportional hazards model. Data from 134 patients (93 males [69.4%] and 41 females [30.6%]) were collected. Median age was 69years (range 36-85), with a median follow-up of 12months (range 1-131). The median body mass index (BMI) was 24.5 (IQR 21.5; 26.1) kg/m2. Overall, 59.0% and 51.5% of patients met established radiographic criteria for evidence of sarcopenia and myosteatosis, respectively, which occur across the BMI spectrum. Multivariate regression analysis, adjusted for co-morbidities, revealed that sarcopenia (aOR 5.56, 95% CI. 2.46-12.6, P<0.0001) and low intermuscular adipose tissue (IMAT) area (aOR 1.83, 95% CI. 1.22-2.83, P=0.001) were associated with a lower rate of ORR (30.4% vs. 70.5%, P<0.0001 and 30.7% vs. 73.2%, P<0.0001, respectively). Moreover, both in univariate and multivariate analysis, adjusted for co-morbidities, low performance status according to the Eastern Cooperative Oncology Group scale (ECOG PS), sarcopenia and low IMAT were significantly related to short PFS (ECOG PS: aHR 2.73, 95% CI 1.60-4.66, P<0.0001; sarcopenia: aHR 2.24, 95% CI 1.37-3.67, P=0.001; IMAT depot: aHR 2.26, 95% 1.40-3.63, P=0.002) and OS (ECOG PS: aHR 3.44, 95% CI 1.96-6.01, P<0.0001; sarcopenia: aHR 4.68, 95% CI 2.44-8.99, P<0.0001; IMAT depot: aHR 3.18, 95% 1.72-5.88, P<0.0001). Skeletal muscle abnormalities, apparently frequent in NSCLC, potentially represent intriguing predictive markers of response to ICIs and survival outcomes. Large prospective trials are needed to validate ICIs responders' clinical biomarkers.

Effect of baseline anemia on the efficacy of docetaxel and ramucirumab for advanced non-small cell lung cancer treatment

BackgroundDocetaxel (DOC) and ramucirumab (RAM) is one of the most effective regimens for advanced non-small cell lung cancer (NSCLC) treatment. In our previous study, baseline anemia was identified as a preventive factor against the development of severe adverse effects during the first treatment cycle. It was hypothesized that anemia directly promotes tumor angiogenesis, leading to the elevation of RAM efficacy with increased DOC delivery to tumors, while reducing DOC delivery to other organs, potentially mitigating severe adverse effects. If this hypothesis is correct, patients with baseline anemia may have better clinical outcomes than those with normal hemoglobin levels. In this study, we aimed to investigate the effect of baseline anemia on the efficacy of DOC + RAM in treating advanced NSCLC in a real-word setting.MethodsPatients with advanced NSCLC receiving DOC + RAM (n = 72) were retrospectively assessed. They were categorized into a control group with normal baseline hemoglobin levels and an anemia group with baseline anemia. The primary endpoint was progression-free survival (PFS) evaluation.ResultsPatients in the anemia group had a significantly shorter PFS than that of patients in the control group (median PFS: 3.2 and 6.2 months; 95% confidence interval [CI]: 2.2–4.8 and 4.3–9.9 months, respectively;P = 0.008). In addition, the disease control rate in the anemia group was 65.8%, which was significantly lower than that in the control group (93.6%; P = 0.007). Overall survival tended to be shorter in patients with anemia than in controls, although the difference was not statistically significant (P = 0.07). Multivariate Cox hazard analysis suggested that baseline anemia was a singular risk factor for poor PFS (adjusted hazard ratio 1.84, 95% CI 1.08–3.13; P = 0.02). The incidence of severe adverse effects did not differ between the two groups.ConclusionsThis study suggests that the PFS of patients with anemia treated with DOC + RAM for advanced NSCLC is shorter than that of those without the symptoms.

Evaluation of a risk-sharing agreement for atezolizumab treatment in patients with non-small cell lung cancer: a strategy to improve access in low-income countries.

Using immune checkpoint inhibitors (IO) is a promising approach to maximize clinical benefits for patients with non-small cell lung cancer (NSCLC). PD-L1 expression serves as a predictive factor for treatment outcomes with IO. However, the high cost of this treatment creates significant barriers to access. Substantial evidence demonstrates the sustained clinical benefits experienced by patients who respond to immunotherapy. While IOs show promise in NSCLC treatment, their high cost poses access barriers. This study focused on a prospective cost analysis conducted at a high-specialty health facility to assess the economic implications of implementing a risk-sharing agreement (RSA) for atezolizumab in NSCLC. The study included 30 patients with advanced NSCLC, with the pharmaceutical company funding the initial cycles. If patients responded, a government program covered costs until disease progression. A median progression-free survival of 4.67 months across populations, rising to 9.4 months for responders. The 2-year overall survival rate for the response group was 64%, significantly higher than for non-response. Without an RSA, a total treatment cost of $881 859.36 ($29 395.31/patient) was reported, compared to $530 467.12 ($17 682.24/patient) with an RSA, representing a 40% cost reduction. In responders, the average cost per year of life per patient dropped by 22%. Risk-sharing, assessed through non-parametric tests, showed a statistically significant difference in pharmacological costs (P < .001). Implementing RSAs can optimize resource allocation, making IO treatment more accessible, especially in low-income countries.

Efficacy and safety of combining radiotherapy with immune checkpoint inhibitors in patients with advanced non-small cell lung cancer: a real-world study

Background The significance of local radiotherapy (RT) in advanced non-small-cell lung cancer (NSCLC) is well documented. However, the advent of immunotherapy has raised questions regarding the synergistic survival benefits or potential adverse effects. Objective This study aimed to explore whether a combination of RT and systematic immune checkpoint inhibitors (ICIs) can improve the survival outcomes for NSCLC patients. Methods Based on collected data patients who received RT were defined as the RT group, and those who had not for any site were defined as the non-RT group. Propensity score matching (PSM) was employed to mitigate bias. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and treatment-related adverse events (AEs). Results Out of 709 patients (235 in RT group and 474 in non-RT group) were included, with 213 patients per group. The median PFS of the RT group was better than that of the non-RT group (13.8 months versus 9.5 months; p < 0.0001), although no superiority in median overall survival (OS) of the RT group was observed (p = 0.715). However, among the cohort of patients with ≤3 metastases, the median OS of the RT group improved significantly (HR = 0.60, [95% CI 0.44–0.83]; p = 0.004). Treatment-related AEs occurred in 94.5% of RT group patients and in 94.9% of non-RT group patients (p = 0.792), which indicated no observable increase in AEs from RT. Conclusions These results demonstrate the tolerability of RT when administered along with immunotherapy, suggesting its potential to positively impact the survival outcomes of NSCLC patients.

Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer

High heterogeneity in clinical benefit characterizes the use of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We prospectively enrolled 113 advanced NSCLC patients treated with ICIs and performed liquid biopsy at the time of ICI start (T1), after 3 weeks (T2) and at the time of radiological evaluation (T3). Molecular variables were associated with outcome endpoints: cfDNA quantification, its dynamic change (∆T2–T1), variant allele frequency (VAF) of the gene with the highest frequency detected at baseline with NGS (maxVAF) and its dynamic change (∆T2–T1). At multivariate analysis, PD-L1 negativity, T1 cfDNA, cfDNA increase (∆T2–T1), and T2 VAF were significantly associated with shorter progression-free survival (PFS); PD-L1 negativity, squamous histology, T1 cfDNA, cfDNA (∆T2–T1) increase, and T2 maxVAF affected overall survival (OS). Among high PD-L1 expressing patients treated in first-line, elevated T2 maxVAF and cfDNA increase (∆T2–T1) correlated with worse PFS; higher T2 maxVAF and cfDNA increase (∆T2–T1) with worse OS. Derived integrated models were used to build nomograms and categorize different risk groups.

Survival Outcomes of Neoadjuvant Therapy Followed by Sleeve Lobectomy in Non-Small Cell Lung Cancer

This study was carried out to evaluate the impact of neoadjuvant therapy on long-term survival in non-small cell lung cancer (NSCLC) patients undergoing sleeve lobectomy. A total of 613 patients were retrospectively analyzed, including 124 who received neoadjuvant therapy. A 1:2 Propensity score matching (PSM) method was adopted to create a balanced cohort including 110 with neoadjuvant therapy and 169 without neoadjuvant therapy. Survival was estimated using the Kaplan-Meier method and compared using the Log-rank test and Cox proportional hazards models. Neoadjuvant therapy was associated with improved 3-year DFS (73.6% vs. 54.4%, P<0.001) and OS (80.9% vs. 63.9%, P=0.002) compared to patients without neoadjuvant therapy. Moreover, neoadjuvant chemoimmunotherapy significantly improved 3-year DFS (85.3% vs. 54.4%, P=0.001) and OS (88.2% vs. 63.9%, P=0.006), whereas chemotherapy alone did not show a significant effect. Multivariable Cox regression analysis revealed that neoadjuvant therapy was an independent predictor of improved DFS and OS while pathological N2 stage was independently associated with poorer DFS and OS. Furthermore, subgroup analysis in the neoadjuvant arm revealed that pathological N2 stage was an independent risk factor for DFS (HR, 3.830; 95% CI, 1.687-8.694; P=0.001), and achieving major pathologic response (MPR) was an independent predictor for better OS (HR, 0.120; 95% CI, 0.015-0.933; P=0.043). Neoadjuvant therapy prior to sleeve lobectomy significantly increased DFS and OS in locally advanced NSCLC. Sleeve lobectomy is advisable followed by neoadjuvant therapy, especially with chemoimmunotherapy.

P1.12B.05 Patient and Oncologist Preferences for ALK+ Advanced Non-Small Cell Lung Cancer Tyrosine Kinase Inhibitor Treatments

P1.12B.05 Patient and Oncologist Preferences for ALK+ Advanced Non-Small Cell Lung Cancer Tyrosine Kinase Inhibitor Treatments

MA11.04 First-in-Class PD-1/IL-2 Bispecific Antibody IBI363 In Patients with Advanced Non-Small Cell Lung Cancer in a Phase I Study

MA11.04 First-in-Class PD-1/IL-2 Bispecific Antibody IBI363 In Patients with Advanced Non-Small Cell Lung Cancer in a Phase I Study

MA16.03 Survival Outcomes in Single Versus Double Immune Checkpoint Inhibitor in Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

MA16.03 Survival Outcomes in Single Versus Double Immune Checkpoint Inhibitor in Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

P1.12A.07 A Phase 1 Study of TY-9591 in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients with EGFR Positive Mutation.

P1.12A.07 A Phase 1 Study of TY-9591 in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients with EGFR Positive Mutation.