Treatment Of Advanced NSCLC Patients Research Articles

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

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

Real-world outcomes of osimertinib in Peruvian patients with advanced NSCLC with EGFR T790M-positive: A multi-institutional experience.

e20605 Background: Osimertinib is the standard of care for advanced NSCLC patients with EGFR T790M-positive whose disease has progressed to EGFR TKI therapy, however, the knowledge on the real benefit of these therapies in the Latin American setting remains unclear due the lack of access in the most countries. The aim of this study is to evaluate the outcomes of Osimertinib as sencond line treatment of advanced NSCLC patients with EGFR T790M-positive in a real-world Peruvian setting. Methods: This is a retrospective study of advanced NSCLC patients with EGFR T790M-positive treated with osimertinib at seven Peruvian institutions between July 2018 and May 2023. Outcomes were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and OS from the start of first-line treatment to death. Results: We analyzed 41 T790M-positive patients with a median age of 60 years (range 36-87y), most of them were females (65.9%), 17.1% had smoking history and 19.5% biomass exposition as a main risk factor. About diagnosis and clinical features, T790M mutation was detected by liquid biopsy in 29.3% of cases, 36 patients (87.8%) had status performance 0 - 1 (ECOG) and 10 (24.4%) presented brain metastases as progression to the previous line of treatment. About outcomes, the ORR was 70.8%; with a median follow-up of 36 months, the median PFS was 15.2 months (95% IC, 9.6 - 20.7) and median OS since the start osimertinib was 16.3 months (95% IC, 7.6 - 24.9), no differences were found regarding the presence of brain metastases (p = 0.06 and p = 0.32) or type of mutation (p = 0.27 and p = 0.46) in both PFS and OS. Median OS from the start of first-line treatment was 46.6 months (95% IC, 34.5 - 58.7). As supplementary analysis, in the same period of time, 11 T790M-positive patients who did not receive osimertinib as second line of treatment achieved a median OS from the start of first-line treatment of 23.5 months (95% IC, 16.5 - 30.5). This OS was significantly lower compared to those who did receive osimertinib (p = 0.001). Conclusions: This study confirms the efficacy of osimertinib in the real world when used as a second line of treatment in T790M-positive patients, in addition the feasibility of osimertinib in this setting may significantly impact the survival.

Immune checkpoint inhibitor (ICI)-based treatment beyond progression with prior immunotherapy in patients with driver-gene negative advanced non-small cell lung cancer

BackgroundNo definite conclusion has yet to be reached for immunotherapy beyond progression(IBP) of first-line immunotherapy as the second-line treatment for advanced NSCLC patients with negative driver genes. Therefore a retrospective study was conducted to evaluate the efficacy of IBP in this population and investigated whether the cycles best response and progressive mode of first-line immunotherapy could affect the results.Patients and methodsThe clinical data of patients with advanced NSCLC whose response was evaluated as progressive disease (PD) after receiving a PD-1/PD-L1 inhibitors as first-line therapy were retrospectively collected and the patients were assigned to the IBP and non-IBP groups. The overall survival (OS), progression-free survival (PFS) were evaluated between the two groups. The survival effects of cycles best response and progressive mode of first-line immunotherapy were also evaluated.ResultsBetween January 2019 and January 2022, a total of 121 patients was evaluated as PD after first-line immunotherapy in our institution; 53 (43.8%) patients were included in the IBP group and 68 (56.2%) patients were included in the non-IBP group. The OS and PFS were no significantly different between the two groups in whole population. Further analysis revealed the OS was prolonged with the prolongation of first-line medication cycle. The median OS was 15.4m (15.4 vs 10.8 p=0.047) 16.1m (16.1 vs 10.8 p=0.039), 16.3m (16.3 vs 10.9 p=0.029) for patients with ≥4, ≥6, ≥8 cycles in first-line immunotherapy, respectively. The advantages of OS and PFS were also seen in the subgroup of PR (best response) and oligo progression of first-line immunotherapy.ConclusionsThe clinical outcomes of IBP were similar to those of non-IBP in patients with PD after first-line immnuotherapy in advanced NSCLC. But more cycles, PR as best response and oligo progression in first-line was benefit.

Abstract 1182: PDC*lung01: An innovative therapeutic cancer vaccine induces specific immune responses in combination with anti- PD-1 treatment in patients with non-small cell lung cancer

Abstract We have developed an innovative cancer vaccine for the treatment of advanced NSCLC patients in combination with checkpoint inhibitors. This PDC*lung01 product based on an irradiated plasmacytoid dendritic cell line loaded with HLA-A*02:01 restricted peptides (NY-ESO-1, MAGE-A3, MAGE-A4, Multi-MAGE-A, MUC1, Survivin and Melan-A) is able to prime and expand peptide-specific CD8+ T cells in vitro and in vivo, and is synergistic with anti-Programmed Death (PD)-1 (Plumas et al, 2022; Hannani et al, 2023, NCT03970746). In study PDC-LUNG-101 with EudraCT number 2018-002382-19, PDC*lung01 is injected intravenously and subcutaneously for 6 times at two dose levels, 14 million, or 140 million cells in stage II/IIIA (cohort A1 & A2, monotherapy) or stage IV with TPS≥50% (cohort B1 & B2; in combination with pembrolizumab) patients. We report here the analysis of immune response of 3 cohorts (A1, A2, B1) of patients and the first 19 patients out of 42 (cohort B2) treated with high dose of PDC*lung01 in combination with Pembrolizumab at baseline and 3 timepoints post injection. Several circulating immune parameters have been evaluated at different times before and after vaccination using different assays we have developed: leukocyte count and determination of circulation peptide specific CD8+ T cells by flow cytometry using multimer tools without prior in vitro culture. The assay made on purified CD8+ T-cells allowed us to define a limit of quantification (LOQ) to accurately assess the fold changes of the cell expansion. In addition, tumor microenvironment (TME) was analyzed by multiplex fluorescence immunochemistry. The data of 42 patients for who an immune response has been evaluated (cohorts A and B) will be presented. No major changes in circulating main lymphocyte frequencies (B cells, NK cells, CD4+, CD8+, or Treg T cells) were observed during treatment. In addition, no major cell activation (CD25+, CD54, or DR+) was noted. In contrast, in a significant number of patients, PDC*lung01 induced circulating peptide-specific CD8+ T cell expansion in all 4 cohorts at different levels and time points against at least one out of seven peptides used. The percentages of patients for who an expansion of antigen-specific T-cell were observed were 50%, 64%, 66.7% and 68.4% in A1, A2, B1 and B2 cohorts respectively. The intensity of the immune response was proportional to the dose of PDC*lung01 and to the combination with pembrolizumab. When possible, total and peptide-specific CD8+ T cells were sorted for analysis of TCR repertoire, illustrating the modelling and dynamics of the immune response. The TME features will also be illustrated. To conclude, treatment with PDC*lung01 induces an anti-tumor immune response in a significant number of patients which appears to be enhanced by the combination with pembrolizumab. Citation Format: Joel Plumas, Anne Sibille, Ingel Demedts, Elvire Pons-Tostivint, Charlotte Van de Kerkhove, Sofie Derijcke, Willemijn Theelen, Bonne Biesma, Frank Borm, Els Wauters, Mike Collodoro, Kays Al Badawy, Camille Duchayne, Channa Debruyne, Beatrice Devos, Benoit Colinet, Denis Moro-Sibilot, Maurice Perol, Eva-Lotte Buchmeier, Marcin Skrzypski, Kristof Cuppens, Johan Vansteenkiste. PDC*lung01: An innovative therapeutic cancer vaccine induces specific immune responses in combination with anti- PD-1 treatment in patients with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1182.

East Asian patients who received immunotherapy-based therapy associated with improved survival benefit in advanced non-small cell lung cancer: An updated meta-analysis.

Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been recommended as the standard treatment for advanced NSCLC patients without driver-gene mutations. However, there are different genetic characteristics and biological traits of tumors between non-East Asian (nEA) and East Asian (EA) patients with NSCLC, which may contribute to differences in the efficacy of ICIs in different ethnic populations. Previous findings regarding differences in the efficacy of ICIs among ethnic groups have been inconsistent. Therefore, we performed a meta-analysis by collecting published data to investigate the clinical outcomes of ICIs for EA NSCLC patients compared to nEA patients. Overall survival (OS) and progression-free survival (PFS) were used to access the difference in survival outcomes between the two populations. Subgroup analyses were performed based on the line of ICIs, the use of ICIs alone or in combination, and the type of ICIs. A total of 9826 NSCLC patients from 21 randomized controlled trials (RCTs) with 4064 EAs were included, which involved PD-1, PD-L1, and CTLA-4 inhibitors. EA NSCLC patients who received ICIs-based therapy were associated with significantly improved survival benefits in OS (p = 0.02) compared with nEA patients. Subgroup analysis indicated that EA patients receiving first-line ICIs showed significantly superior OS compared with nEA patients (p = 0.007). Chemo-ICIs treatment showed significant advantages in terms of OS (p = 0.002) and PFS (p = 0.02) among EA patients compared to nEA patients. In addition, PD-1 inhibitors were associated with improved OS among both EA patients and nEA patients compared with PD-L1 inhibitors. EA NSCLC patients who received ICIs-based therapy were associated with significantly improved survival benefits compared with nEA NSCLC patients. Earlier intervention with ICIs and combination treatment was more recommended for EA NSCLC patients. Moreover, PD-1 inhibitors are associated with prolonged survival among both EA and nEA patients.

EP12.02-09 Prevalence and Treatment of Advanced NSCLC patients with REarranged During Transfection [RET]-fusion at a South Korean Centre

EP12.02-09 Prevalence and Treatment of Advanced NSCLC patients with REarranged During Transfection [RET]-fusion at a South Korean Centre

EP12.01-77 Real-word Study of Aumolertinib Treatment for Advanced NSCLC Patients with Uncommon EGFR Mutations in Late Permian Coal Area

EP12.01-77 Real-word Study of Aumolertinib Treatment for Advanced NSCLC Patients with Uncommon EGFR Mutations in Late Permian Coal Area

Impact of BMI on the survival outcomes of non-small cell lung cancer patients treated with immune checkpoint inhibitors: a meta-analysis

ObjectivesICIs have become the standard treatment for advanced NSCLC patients. Currently, PD-L1 is the most widely useful biomarker to predict ICI efficacy, but the sensitivity and specificity are limited. Therefore, the useful predictive biomarkers of ICI efficacy is urgently needed. BMI is an internationally used measure of body health. Obesity may affect ICI efficacy by changing T cell functions. This meta-analysis aimed to clarify the relationship between BMI and survival outcomes of NSCLC patients treated with ICIs.MethodsA systematic review was conducted to identify studies that assessed the association between BMI and survival outcomes in patients treated with ICIs. OS was the primary endpoint, and PFS was the secondary endpoint. Random-effect models or fixed-effect models were utilized to combine study effects according to the Cochran Q and I2 tests.ResultsNine studies, including 4602 NSCLC patients treated with ICIs, that met the inclusion criteria were selected for this meta-analysis. There was no significant difference in PFS (HR 0.885; 95% CI 0.777–1.009, p = 0.068) or OS (HR 0.947; 95% CI 0.789–1.137, p = 0.560) between the low BMI group and the high BMI group. However, in the subgroup analysis, compared with normal-weight patients, overweight and obese patients achieved prolonged PFS (HR 0.862; 95% CI 0.760–0.978, p = 0.021) and OS (HR 0.818; 95% CI 0.741–0.902, p<0.0001).ConclusionOverweight and obese NSCLC patients tend to achieve prolonged survival time with ICI regimens. Further prospective studies are needed to strengthen the association between ICI outcomes and BMI levels.

A decision-making tool for first-line treatment in advanced non–small-cell lung cancer based on plasma proteome biomarkers.

9122 Background: Initial treatment selection for advanced NSCLC patients without driver mutations is mainly based on evaluating PD-L1 expression levels in the tumor tissue. However, PD-L1 assays are only moderately predictive. In addition, the guidelines for the PD-L1≥50% subpopulation are not definitive, enabling the usage of immune checkpoint inhibitors (ICI) either as a monotherapy or combined with chemotherapy. Here we aim to provide a decision-making tool for the first-line treatment of advanced NSCLC patients based on plasma derived biomarkers obtained before treatment initiation. Methods: Pre-treatment plasma samples were collected from 545 NSCLC patients receiving ICI-based therapy. Clinical benefit was evaluated based on progression-free survival (PFS) at 12 months as a threshold. Deep plasma proteomic profiling was performed using aptamer technology. Based on the proteomic profiles, a computational model, termed PROphet, was developed and evaluated in a blinded manner on the validation subset (n = 272). The model output, clinical benefit probability, was used to stratify the patients into two groups, PROphet-positive or -negative. Results: The model displayed good performance with a high correlation between the predicted clinical benefit and the observed clinical benefit rate (R2= 0.97), outperforming a PD-L1-based prediction model (R2= 0.35). Patients classified as PROphet-positive achieved significantly longer overall survival (OS) than PROphet-negative patients, with a median OS of 25.9 versus 10.8 months (hazard ratio, HR = 0.51; 95% confidence interval, CI = 0.37-0.70; p-value &lt; 0.001). Next, we examined the clinical utility of combining the PROphet output with PD-L1 levels by comparing different treatment modalities. Focusing on PD-L1≥50%, patients with PROphet-positive results displayed similar OS and PFS when receiving ICI monotherapy or ICI-chemotherapy (OS HR = 0.77; CI = 0.42-1.43; p-value = 0.4096), suggesting that these patients may consider monotherapy, thus avoiding chemotherapy-related toxicity. Conversely, PD-L1≥50% patients with a PROphet-negative result displayed a significantly longer OS and PFS when receiving ICI-chemotherapy in comparison to ICI monotherapy, with a median OS that was not reached versus 11.10 months in the combination therapy and monotherapy groups, respectively (HR = 0.29; CI = 0.14-0.59; p-value &lt; 0.001). These patients should consider combination therapy, avoiding a treatment that is suboptimal for them. Results for PD-L1 1-49% and &lt; 1% provide additional clinical information for each subgroup. Conclusions: Plasma proteomic profiling can provide biomarkers that accurately predict the benefit of ICI-based treatment. The model output complements tissue PD-L1 expression levels as a tool to assist therapeutic decisions.

Clinical outcomes for immunotherapy beyond progression in patients with advanced non-small cell lung cancer.

e21222 Background: No definite conclusion has yet to be reached for immunotherapy beyond progression(IBP)as the second-line treatment for advanced NSCLC patients with negative driver genes. Therefore, a retrospective study was conducted to evaluate the efficacy of IBP in this population and investigated whether the cycles, best response and progressive mode of first-line immunotherapy could affect the results. Methods: The clinical data of patients with advanced NSCLC whose response was evaluated as progressive disease (PD) after receiving a PD-1/PD-L1 inhibitors as first-line therapy were retrospectively collected and the patients were assigned to the IBP and non-IBP groups. The overall survival (OS), progression-free survival (PFS) were evaluated between the two groups. The survival effects of cycles, best response and progressive mode of first-line immunotherapy were also evaluated. Results: Between January 2019 and January 2022, a total of 121 patients was evaluated as PD after first-line immunotherapy in our institution; 53 (43.8%) patients were included in the IBP group and 68 (56.2%) patients were included in the non-IBP group. The OS and PFS were no significantly different between the two groups. Further analysis revealed the OS was prolonged with the prolongation of first-line medication cycle. The median OS was 15.4m (15.4 vs 10.8 p= 0.029), 16.1m (16.1 vs 10.8 p= 0.021), 16.3m (16.3 vs 10.9 p= 0.015) for patients with ≥4, ≥6, ≥8 cycles in first-line immunotherapy, respectively. The advantages of OS and PFS were also seen in the subgroup of PR (best response) and local progression of first-line immunotherapy. Conclusions: The clinical outcomes of IBP were similar to those of non-IBP in patients with PD after first-line immnuotherapy in advanced NSCLC. But more cycles, PR as best response and local progression in first-line was benefit.

Effect of bevacizumab plus double dose icotinib on advanced non-small cell lung cancer with EGFR L858R mutation.

e21020 Background: Double-dose icotinib has been proven effective and well tolerated for advanced NSCLC patients with the Epidermal Growth Factor Receptor (EGFR) L858R mutation. For the same patients, the excellent efficacy of bevacizumab combined with erlotinib has been proven in previous studies. In this study, we would investigate the efficacy of the combined therapy bevacizumab and double-dose icotinib for advanced NSCLC patients with EGFR L858R mutation. Methods: 35 patients diagnosed from September 2, 2021 to September 28, 2022 were enrolled in this study and 5 patients were excluded for analysis due to missing efficacy evaluation data. All patients were treated with intravenous bevacizumab (15mg / kg) combined with oral double-dose icotinib (250mg, tid). The primary endpoint was progression-free survival (PFS), and the secondary endpoints were safety, efficacy, and overall survival (OS). Results: Among the 35 patients, 12 were male and 23 were female. The median age at diagnosis was 66. Eight patients were diagnosed with brain metastases. All of the patients have EGFR L858R mutation, and 14 patients were with other coexisting mutations. To the data of December 31, 2022, the median follow-up time was 10 months (range: 3 to 18 months). For 30 patients with complete efficacy evaluation data, 20 patients achieved partial responses (PR), 9 patients had stable disease (SD), and 1 patient developed progress disease (PD). The objective response rate (ORR) was 66.7%, the disease control rate (DCR) was 96.7%, and the median PFS was 14.8 months. For adverse reaction evaluation, the grade 3 adverse events were albuminuria (n = 1) and hepatotoxicity (n = 1). Other adverse events were grade 1-2, mainly oral mucositis, rash, diarrhea and hypertension. Conclusions: The combination of bevacizumab with double-dose icotinib is an effective and relatively safe treatment for advanced NSCLC patients with EGFR L858R mutation. Further exploration will provide more evidence for this type of treatment. Clinical trial information: NCT05263947 .

766P Levels of serum EGF concentration as biomarker of response of CIMAvax-EFG vaccine: Survival evaluation of advanced NSCLC patients treated in primary health care scenario

Previous studies have shown that baseline concentrations of EGF in serum could be considered a biomarker of the efficacy of the therapeutic vaccine CIMAVax-EGF. The objective of this study is to evaluate the serum EGF concentration as biomarker of response of CIMAvax-EGF vaccine for the treatment of advanced NSCLC patients in primary health care scenario.

EP08.01-014 Tislelizumab versus Docetaxel in Previously Treated Advanced Non-Small Cell Lung Cancer: Final Analysis of RATIONALE-303

In RATIONALE-303 (NCT03358875) tislelizumab significantly improved OS vs docetaxel in the ITT population at the interim analysis (IA), based upon which, tislelizumab was approved in China for treatment of advanced NSCLC patients with progressive disease after chemotherapy. Here, we report outcomes of the final analysis (FA) and post hoc biomarker analysis.

Development and Validation of a UHPLC-MS/MS Method for Quantitation of Almonertinib in Rat Plasma: Application to an in vivo Interaction Study Between Paxlovid and Almonertinib.

Almonertinib was approved for the first-line treatment of advanced NSCLC patients with EGFR-TKI-sensitive genetic mutations by National Medical Products Administration (NMPA) in 2021.The purpose of this study was to establish and validate a fast, accurate, stable and facile ultra-performance liquid chromatography-tandem mass spectrometry method for the quantification of almonertinib in rat plasma, it was employed to explore the effect of Paxlovid on the pharmacokinetics of almonertinib in rats. Zanubrutinib was used as an internal standard (IS), and the plasma samples were prepared by the protein precipitation method using acetonitrile. Chromatographic separation was carried out on a Shimadzu LC-20AT ultra-performance liquid chromatography system using a Shim-pack velox C18 (2.1× 50 mm, 2.7 μM) column. The mobile phase consisted of methanol and 0.1% formic acid-water. Mass spectrum analysis was executed using Shimadzu 8040 Triple quadrupole mass spectrometry. The precursor and product ions of the analyte and internal standard were detected in multiple reaction monitoring (MRM) mode. The typical fragment ions were m/z 526.20 → 72.10 for almonertinib and m/z 472.15 → 290.00 for zanubrutinib (IS). The method was validated to have good linearity for quantifying almonertinib in rat plasma from 0.1–1000 ng/ml (R2 = 0.999), and the LLOQ was 0.1 ng/ml. The validity of this method was sufficiently verified for selectivity, specificity, extraction recovery, matrix effect, accuracy, precision and stability. The validated UHPLC–MS/MS method was successfully applied to the drug interaction study of almonertinib with Paxlovid in rats. Paxlovid significantly inhibits the metabolism of almonertinib and increased the exposure of almonertinib. This study can help us to understand the metabolic profile of almonertinib better, and further human trials should be conducted to validate the results.

The efficacy of adding hyperthermia to the treatment of advanced NSCLC patients based on the states of EGFR.

Background: The study aims to explore the efficacy of adding hyperthermia to the treatment of advanced NSCLC patients based on the states of epidermal growth factor receptor (EGFR).Patients and methods: We included 205 advanced NSCLC patients who were received hyperthermia plus other treatment (hyperthermia group) or non- hyperthermia and other treatments (non- hyperthermia group). The OS and progression free survival (PFS) were retrospectively estimated. Using Kaplan-Meier and the log-rank test compare the OS and PFS between the groups.Results: The median follow-up was 22 months. The Univariate analysis have shown that 1-year OS and PFSfirst rates in the hyperthermia group and non- hyperthermia group were 83.3% vs 71.5% (P=0.010) and 62.0% vs 42.7% (P=0.001). The subgroup analyses revealed that patients didn’t have EGFR mutant who received hyperthermia had significantly higher 1 year OS and PFSfirst rates than those treated with non- hyperthermia (OS: 79.1% vs 65.2% P=0.037, PFS: 64.2% vs 36.5%, P=0.001). For patients with EGFR mutation, there was no significant difference between the two groups. The PFSfirst in first-line and PFSpost in posterior-line was no significant difference between the groups.Conclusions: This retrospective study revealed that adding hyperthermia to the treatment of NSCLC patients without EGFR mutation had better prognosis than those who did not adding hyperthermia to the regimen. Moreover, adding hyperthermia in first-line or in posterior-line treatment was no significant difference. However, these results need more prospective studies to confirm the conclusions.

Genomic profile by liquid biopsy of Peruvian patients with lung cancer.

e15027 Background: The optimal treatment of advanced NSCLC patients is currently led by genomic profiling with the goal of detecting actionable mutations with an approved targeted therapy. However, tissue DNA samples are not always available to perform this assays. In this context, liquid biopsy has emerged as a valuable tool for providing the best treatment option. Methods: Retrospective study held at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima - Peru, between January 2019 and September 2021 to assess the genomic profile of 190 newly diagnosed advanced NSCLC patients through liquid biopsy. Blood samples were profiled with the FoundationOne Liquid Biopsy assay. We describe frequency of pathogenic and targetable genetic alterations, as well as the survival outcomes. Genomic and clinical data were recorded from clinical files. Results: The median age was 63 years (26-90), 66.3% were women, 15.3% smokers, 26.3% had exposure to biomass, 22.6% had a first-degree family history of cancer. The most frequent histological type was adenocarcinoma (86.8%). Regarding genomic profile, 183 patients (96.3%) had at least one pathogenic genetic alteration, the most frequent altered genes were TP53 (54.7%), EGFR (50.5%), DNMT3A (17.9%), KRAS (9.5%) and NF1 (6.8%). 116 patients (61%) had a targetable mutation: EGFR Ex19del/ins (27.4%), EGFR L858R/L861Q (17.9%), ALK rearrangements (5.8%), BRAF V600E (3.2%), RET fusions (1.6%), METex14 skipping (1.6%), KRAS G12C (1.6%), ROS 1 (1.1%), and NTRK (0.5%). Of these, 71 patients (65.5%) were able to access target therapy. For the latter, estimated median PFS and OS were 14.0 months (9.3 – 18.6) and 17.8 months (8.2 – 27.4), respectively. Conclusions: Peruvian NSCLC patients represent a population with a high frequency of pathogenic and targetable mutations, being EGFR mutations and ALK rearrangements the most prevalent ones. Despite limited access, a great proportion of patients received target therapy, achieving remarkable survival.

Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Progress, Challenges, and Prospects.

Non-small cell lung cancer is one of the most common types of malignances worldwide and the main cause of cancer-related deaths. Current treatment for NSCLC is based on surgical resection, chemotherapy, radiotherapy, and targeted therapy, with poor therapeutic effectiveness. In recent years, immune checkpoint inhibitors have applied in NSCLC treatment. A large number of experimental studies have shown that immune checkpoint inhibitors are safer and more effective than traditional therapeutic modalities and have allowed for the development of better guidance in the clinical treatment of advanced NSCLC patients. In this review, we describe clinical trials using ICI immunotherapies for NSCLC treatment, the available data on clinical efficacy, and the emerging evidence regarding biomarkers.

Ideal sequencing in Stage IV epidermal growth factor receptor mutant Non-Small-Cell Lung Cancer.

Evidence from several studies has shown improved progression-free survival (PFS) with first- or second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) compared with chemotherapy for advanced NSCLC patients. But resistance to first or second-generation TKI therapies after 9 to 12 months of treatment initiation is a concern. Osimertinib is a third-generation, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFRm (epidermal growth factor receptor mutated) and EGFR T790M and has demonstrated efficacy in NSCLC central nervous system (CNS) metastases. Trials have reported significantly longer PFS and higher median duration of response with osimertinib compared with first-generation EGFR-TKIs (erlotinib, gefitinib) and chemotherapy, respectively. And relatively lower rates of discontinuation due to adverse events (AEs). Significant improvement in overall survival was also observed when used as first-line treatment. Because EGFR-mutated tumors are highly dependent on EGFR signaling, optimal sequence of available TKIs - erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib - is necessary. The sequencing of EGFR-TKIs has changed over the past decade and depends on factors such as expected efficacy, CNS activity, tolerability, and options available after progression. Third-generation TKI may be the preferred first-line treatment because patients may not opt for or die before the start of second-line therapy, and it is difficult to predict which patients will eventually develop T790M mutation. The favorable tolerability profile alongside a longer time to disease progression makes osimertinib a preferred first-line treatment. Though clinical practice guidelines do not provide clear consensus on the most preferred EGFR-TKI, recent updates recommend osimertinib as a first-line treatment for advanced NSCLC patients. Also, improved patient selection incorporating clinical and molecular characteristics will help translate to better survival outcomes and improved quality of life. This review aims to determine the optimal sequence of administration of the EGFR-TKIs considering toxicity, quality of life, and survival outcomes among advanced NSCLC patients.

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis.

This network meta-analysis (NMA) evaluates the safety of first-line programmed death-ligand 1 (PD-L1) inhibitor monotherapy in advanced NSCLC patients compared to platinum-based chemotherapy. We also compared the risk of adverse events (AEs) according to programmed cell death-1 receptor (PD-1) or PD-L1 inhibitors therapy. To that end, we conducted a series of metanalyses (MAs) using data from six phase III clinical trials, including 4053 patients. Our results show a reduced risk of any grade treatment-related AEs (risk ratio (RR) = 0.722 95% CI: 0.667–0.783, p = 0.002), and grade 3–5 AEs (RR = 0.406 95% CI: 0.340–0.485, p = 0.023) in immunotherapy as compared to chemotherapy. In contrast, a higher risk of immune-related AEs (irAEs) was estimated for immunotherapy versus chemotherapy. The subgroup MAs comparing PD-L1 to PD-1 inhibitors, determined a lower risk of AEs leading to treatment discontinuation in the anti-PD-L1 subgroup (RR = 0.47 95% CI: 0.29–0.75, p = 0.001); however, this statistically significant difference between anti-PD-L1 and anti-PD-1 subgroups was not reached for other safety outcomes analyzed. In conclusion, our findings show that PD-L1 inhibitor monotherapy improves safety outcomes in the 1L treatment of advanced NSCLC patients as compared to chemotherapy except for irAEs.

P86.23 Clinical Efficacy Analysis of Apatinib as a Second-Or Further-Line Treatment in Patients With Advanced NSCLC

Angiogenic agents play an important role in the therapeutic strategy for advanced NSCLC. Apatinib is a novel tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. The purpose of this study was to collect data on the clinical efficacy and side effects of oral apatinib as a second-or further-line in patients with advanced NSCLC in the first hospital of Jilin University. A total of 43 patients with advanced NSCLC who were hospitalized in the Cancer Center of the First Hospital of Jilin University from January 1, 2017 to December 31, 2018 were enrolled. This study included patients whose initial dose was apatinib 500mg per day. Statistical analysis was performed using the SPSS19.0 system. The Kaplan-Meier method was used for survival analysis and the COX proportional hazard model was used for single factor analysis. The difference was statistically significant at p<0.05. Among all patients, the objective response rate (ORR) is 11.6% and the disease control rate (DCR) is 72.1%. The median progression-free survival (PFS) was 3.7 months. The ORR and DCR of 30 patients with Eastern Cooperative Oncology Group (ECOG) score of 0-1 were 16.7% and 83.3%, respectively, and the median PFS was 5.4 months (95% CI 3.1-7.7 months). The ORR and DCR of 13 patients with ECOG score of 2 were 0 and 4.6%, respectively, and the median PFS was 2.7 months (95% CI 2.1-3.3 months). The difference between the two groups was statistically significant (P=0.012). The most common treatment-related AEs were hypertension (48.8%), hand-foot syndrome (39.5%), diarrhea was (18.6%), nausea and vomiting (18.6%), and the incidence of grade 3 to 4 adverse reactions was 9.3%. Apatinib is convenient, effective and safe in the treatment of advanced NSCLC patients, and the incidence of adverse reactions is low and controllable. ECOG score is the influencing factor of median PFS. For patients with ECOG score of 0-1, oral apatinib 250mg per day therapy can show a better therapeutic effect.