Despite chemo-immunotherapy has been applied to the neoadjuvant treatment of non-small cell lung cancer (NSCLC), the impacts of dosage and the order of medication on treatment efficacy and safety remain largely unexplored. We originally designed an exploratory study to investigate the efficacy and safety of reduced-dose chemotherapy combined with delayed immunotherapy as well as the dynamic changes of circulating tumor DNA (ctDNA) and T cell receptor (TCR) during the therapy.Patients with clinical stage IIA to IIIA resectable NSCLC were treated with 2 cycles of reduced-dose platinum-based chemotherapy on day 1 combined with immunotherapy on day 5. The same postoperative modified adjuvant therapy regimen was administered for 2 cycles. Plasma samples at different time-points were collected and performed with T cell receptor (TCR) and circulating tumor DNA (ctDNA) sequencing.38 patients received modified chemo-immunotherapy. The proportion of patients exhibiting complete response and partial response was 5.3% and 68.4%, respectively. The confirmed objective response rate was 73.7%. Radiological downstaging was achieved in 39.5%. Major pathologic response and complete pathologic response were observed in 47.4% and 31.6% of patients, respectively. Only one patient experienced grade 3 adverse event. Further analyses revealed that this modified chemo-immunotherapy led to the expansion of predominant TCR clones and reduction of tumor burden after the first cycle of chemotherapy.The promising clinical efficacy and low side effects of modified neoadjuvant chemo-immunotherapy position it as a prospective and innovative strategy for NSCLC.

Extensive-stage small cell lung cancer (ES-SCLC) is characterized by a high risk of malignancy and a poor prognosis. This trial aimed to evaluate the efficacy and safety of envafolimab plus chemotherapy as a first-line treatment for ES-SCLC. This prospective, single-arm, phase II trial was conducted at the Fifth Medical Center of Chinese PLA General Hospital. Eligible patients with histologically or cytologically confirmed ES-SCLC were consecutively enrolled. Patients were given four cycles of carboplatin (area under the curve of 5–6 mg/mL/min, day 1 of each cycle) and etoposide (80–100 mg/m2 of body-surface area, on day 1–3 of each cycle) with envafolimab (300 mg, Q3W, day 3 post-chemotherapy of each cycle), followed by envafolimab maintenance until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Between October 2021 and November 2022, a total of 32 patients were enrolled in this trial. A total of 32 patients were included in the safety analysis, and 31 patients were included in the efficacy analysis. As of the data cutoff (September 15, 2024), the median follow-up was 27.7 months (IQR, 22.6–NA). The objective response rate (ORR) was 87.1

We aimed to investigate the genomic and immune microenvironmental characteristics and their prognostic value in limited-stage small cell lung cancer (SCLC). Whole exome sequencing and multiplex immunofluorescence analysis were conducted on 38 patients diagnosed with limited-stage SCLC. The two most frequently mutated cancer-related genes observed were RB1 (73.68%) and TP53 (63.16%). However, none of the cancer-related genes, including RB1 and TP53, were associated with prognosis. Furthermore, genomic factors such as tumor mutation burden, copy number instability, and mutant-allele tumor heterogeneity were unrelated to prognosis. Approximately 52.63% (20/38) of cases exhibited PD-L1 expression (combined positive score > 1). The average percentage of CD8-positive tumor-infiltrating lymphocytes (TILs) was 3.27%, with a range spanning from 0.04 to 18.96%. Survival analyses showed that PD-L1 positivity, a high proportion of CD8-positive TILs, and wild-type PI3K pathway were significantly associated with better survival. A predictive prognostic model was further developed based on these three biomarkers, resulting in more accurate stratification of patients according to disease-free survival (DFS, hazard ratio (HR) = 2.020, P < 0.001) and overall survival (OS, HR = 2.344, P < 0.001). Moreover, PD-L1 negative patients who did not undergo adjuvant chemotherapy exhibited significantly improved OS (P = 0.029) and a favorable trend in DFS (P = 0.053) compared to those who underwent adjuvant chemotherapy. In conclusion, this study analyzed the genomic and immune microenvironment characteristics of limited-stage SCLC and constructed a prognostic model based on PD-L1 expression, CD8-positive TILs, and PI3K pathway mutation, which may potentially contribute to the clinical management of limited-stage SCLC. Clinical trial number: Not applicable.

8090 Background: Extensive-stage small cell lung cancer (ES-SCLC) is related to high malignancy and the poor prognosis. At present, immunotherapy combined with chemotherapy resulted in favorable therapeutic efficacy, and had been established as the standard treatment regimen for first-line treatment of ES-SCLC. However, some patients may still experience intolerable AEs over the course of treatment, such as immune-related pneumonitis and enteritis. Additionally, currently marketed ICIs were administered by continuous intravenous infusion, which is inconvenient for patients. This trial aimed to evaluate the efficacy and safety of envafolimab, which is a subcutaneously administered fusion protein of humanized anti-PD-L1 monodomain antibody, plus chemotherapy as a first-line treatment for ES-SCLC. Methods: This prospective, single-arm, phase II trial was conducted at the Fifth Medical Center of Chinese PLA General Hospital. Eligible patients with histologically or cytologically confirmed ES-SCLC were consecutively enrolled. Patients were given four cycles of carboplatin (5-6 mg/mL/min, day 1 of each cycle) and etoposide (80-100 mg/m², days 1-3 of each cycle) with envafolimab (300 mg, Q3W, day 3 post-chemotherapy of each cycle), followed by envafolimab maintenance until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS), and the secondary endpoint included objective response rate (ORR), disease control rate (DCR), and safety. Results: Between October 2021 and November 2022, a total of 32 patients were enrolled in this study. 32 patients were included for safety analysis, and 31 patients were included for efficacy analysis. As of the data cutoff (September 15, 2024), the median follow-up was 27.7 months. The ORR was 87.1% (95% CI, 70.2-96.4%), and the DCR was 100% (95% CI, 88.8-100%). The median DoR was 5.47 months (95% CI, 3.43-10 months). The median PFS was 6.43 months (95% CI, 4.83-7.67 months), and median OS was 20 months (95% CI, 14.7-NA). Treatment-related adverse events (TRAEs) of any grade were reported in 59.4% of patients, with grade ≥ 3 TRAEs in 15.6% patients. No treatment-related deaths occurred. Conclusions: First-line envafolimab in combination with carboplatin and etoposide yielded favorable clinical efficacy with a manageable safety profile for patients with ES⁃SCLC, representing a promising treatment modality. Clinical trial information: ChiCTR2100044981 .

This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95

BackgroundPenpulimab is a novel programmed death (PD)-1 inhibitor. This study aimed to establish the efficacy and safety of first line penpulimab plus chemotherapy for advanced squamous non-small-cell lung cancer.MethodsThis multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial enrolled patients with locally advanced or metastatic squamous non-small-cell lung cancer from 74 hospitals in China. Eligible participants were aged 18–75 years, had histologically or cytologically confirmed locally advanced (stage IIIb or IIIc) or metastatic (stage IV) squamous non-small-cell lung cancer, were ineligible to complete surgical resection and concurrent or sequential chemoradiotherapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, did not have previous systemic chemotherapy for locally advanced or metastatic non-small-cell lung cancer, and had one or more measurable lesions according to RECIST (version 1.1). Participants were randomly assigned (1:1) to receive intravenous penpulimab 200 mg or placebo (excipient of penpulimab injection), plus paclitaxel 175 mg/m2 and carboplatin AUC of 5 intravenously on day 1 every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy. Stratification was done according to the PD-L1 tumour proportion score (<1% vs 1–49% vs ≥50%) and sex (male vs female). The participants, investigators, and other research staff were masked to group assignment. The primary outcome was progression-free survival assessed by the masked Independent Radiology Review Committee in the intention-to-treat population and patients with a PD-L1 tumour proportion score of 1% or more (PD-L1-positive subgroup). The primary analysis was based on the intention-to-treat analysis set (ie, all randomly assigned participants) and the PD-L1-positive subgroup. The safety analysis included all participants who received at least one dose of study drug after enrolment. This trial was registered with ClinicalTrials.gov (NCT03866993).FindingsBetween Dec 20, 2018, and Oct 10, 2020, 485 patients were screened, and 350 participants were randomly assigned (175 in the penpulimab group and 175 in the placebo group). Of 350 participants, 324 (93%) were male and 26 (7%) were female, and 347 (99%) were of Han ethnicity. In the final analysis (June 1, 2022; median follow-up, 24·7 months [IQR 0–41·4]), the penpulimab group showed an improved progression-free survival compared with the placebo group, both in the intention-to-treat population (median 7·6 months, 95% CI 6·8–-9·6 vs 4·2 months, 95% CI 4·2–4·3; HR 0·43, 95% CI 0·33–0·56; p<0·0001) and in the PD-L1-positive subgroup (8·1 months, 5·7–9·7 vs 4·2 months, 4·1–4·3; HR 0·37, 0·27–0·52, p<0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 120 (69%) 173 patients in the penpulimab group and 119 (68%) of 175 in the placebo group.InterpretationPenpulimab plus chemotherapy significantly improved progression-free survival in patients with advanced squamous non-small-cell lung cancer compared with chemotherapy alone. The treatment was safe and tolerable. Penpulimab combined with paclitaxel and carboplatin is a new option for first-line treatment in patients with this advanced disease.FundingThe National Natural Science Foundation of China, Shanghai Municipal Health Commission, Chia Tai Tianqing Pharmaceutical, Akeso.

e20564 Background: In recent years, treatment for advanced or metastatic NSCLC has been significantly improved with the emergence of a combination strategy of immunotherapy with antiangiogenic drugs plus chemotherapy. Although endostatin (an antiangiogenic agent) combined with chemotherapy has been approved by the China Food and Drug Administration in treatment-naïve and re-treatment NSCLC patients, the clinical evidence supporting its combination with programmed cell death-1 (PD-1) antibody for advanced or metastatic NSCLC is still insufficient. Therefore, we aimed to evaluate the effectiveness and safety of endostatin combined with PD-1 antibody plus chemotherapy as the first-line treatment for locally advanced or distant metastatic NSCLC with EGFR/ALK-negative. Methods: This was a retrospective, singer-center, real-world study conducted between June 2018 and December 2021. The primary endpoint was progression-free survival (PFS); the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: Overall, 68 patients were included. The median PFS and OS were 22.0 months (95% confidence interval [CI]: 16.6-27.4 months) and 31.0 months (95% CI: 23.4 months-not reached [NR]), respectively, with a median follow-up of 21.4 months (range, 8.3-44.4 months). At the data cutoff, 33 patients (48.5%) remained progression-free and 24 patients (35.3%) had died. Short-term clinical efficacy was assessed after 2 consecutive treatment cycles, with an ORR of 72.06% (complete response [CR], n = 3; partial response [PR], n = 46) and a DCR of 95.59% (CR, n = 3; PR, n = 46; stable disease, n = 16). Further subgroup analysis determined that a significantly better ORR (89.2% vs. 51.6%), median PFS (23.4 vs. 13.2 months), and median OS (NR vs. 18.0 months) for patients with stage Ⅲ B/Ⅲ C vs. stage Ⅳ NSCLC (all p ≤ 0.001). Besides, the median PFS (8.0 months vs. 22.5 months, p = 0.004) and OS (13.0 vs. 31.0 months, p = 0.027) of patients with brain metastasis were significantly shorter than those without brain metastasis. The ORR in patients who had a PD-L1 tumor proportion score (TPS) of < 1%, 1%-49%, ≥ 50%, and unknown were 50%, 50%, 75.0%, and 86.1%, respectively ( p = 0.025). All patients (100%) experienced treatment-related adverse events (AEs). The majority of AEs were grade 1 or 2 (57/68, 83.82%). Conclusions: In the real-world scenario, endostatin combination with PD-1 antibody plus chemotherapy obtained encouraging efficacy and favorable safety in advanced or metastatic NSCLC. The combination strategy in this study furnished beneficial evidence for the treatment of advanced or metastatic NSCLC and is essential for determining the best treatment option.

Background Immune checkpoint inhibitors (ICIs) have changed the treatment landscape of several cancer types. However, data are lacking with regard to the clinical responsiveness of ICIs in patients with advanced non-small cell lung cancer (NSCLC) after standard first-line chemotherapy. Therefore, we aimed to evaluate the clinical efficacy of ICI alone or in combination with chemotherapy for patients with advanced NSCLC after first-line platinum-based chemotherapy. Methods We retrospectively collected patients with confirmed advanced NSCLC who underwent ICI monotherapy or ICI plus chemotherapy after first-line platinum-based chemotherapy between January 2018 and December 2020. A propensity score matching analysis was used to balance baseline characteristics between the two treatment groups. Kaplan-Meier methods and multivariable Cox regressions were used for survival analyses. Results Among 832 eligible patients, 222 received ICI monotherapy and 610 received ICI plus chemotherapy. The median overall survival (OS) of patients who received ICI plus chemotherapy was 16.0 months compared with 13.1 months in patients who received ICI monotherapy (HR: 0.64, 95% CI: 0.49-0.85, P = 0.002). After 1:1 propensity score matching, all baseline characteristics were well-balanced between the two treatment groups. Patients who received ICI plus chemotherapy had significantly longer OS than those who received ICI monotherapy (NR vs. 13.1 months, HR: 0.50, 95% CI: 0.34-0.71, P < 0.001). Meanwhile, the median time to treatment discontinuation was 4.4 months in the ICI-chemo group and 3.5 months in the ICI-mono group (HR: 0.72, 95% CI: 0.58-0.89, P = 0.002). The multivariate analysis indicated that treatment regimen was an independent prognostic factor for OS (HR: 0.488, 95% CI: 0.337-0.707, P < 0.001). Moreover, a nomogram that integrated both treatment regimens and clinicopathological factors was created for survival prediction. Conclusion Our study indicated that patients with advanced NSCLC who received ICI plus chemotherapy after first-line platinum-based chemotherapy tended to have longer OS than those who received ICI monotherapy. The multivariate analysis showed that treatment regimen was an independent prognostic factor for OS. Future prospective studies are needed to confirm these findings.

Aims: This trial explored the safety and efficacy of neoantigen-specific T cells (Nas-Ts) combined with anti-PD-1 (Nas-T + anti-PD-1). Patients & methods: This non-randomized trial recruited participants with solid tumors treated with at least two prior systemic treatment lines. For comparison, 1:1-matched controls who received anti-PD-1 alone were recruited. The primary end point was safety. Results: 15 participants were enrolled in the Nas-T + anti-PD-1 group, the objective response rate was 33.3%, and the disease control rate was 93.3%. The median progression-free survival was significantly different between the Nas-T + anti-PD-1 and control groups (13.8 vs 4.2 months; p = 0.024), but no difference in overall survival was found (p = 0.126). The most common adverse events were maculopapular skin reaction (53.3%), rash (53.3%), hepatotoxicity (53.3%) and fever (53.3%) in the Nas-T + anti-PD-1 group. No serious safety issues were experienced. Conclusion: Nas-Ts combined with anti-PD-1 could be more effective than anti-PD-1 alone in prolonging progression-free survival, with good safety.

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC. METHODS This multicenter, open-label, pilot randomized controlled trial enrolled 68 EGFR-mutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy + icotinib groups. RESULTS The median progression-free survival in the icotinib alone and chemotherapy + icotinib groups was 8.0 mo (95%CI: 3.84-11.63) and 13.4 mo (95%CI: 10.18-16.33), respectively (P = 0.0249). No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen (all P > 0.05). CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

目的:观察三种营养制剂对接受化疗的肺癌及乳腺癌患者外周血免疫相关细胞因子表达谱的影响,为抗癌辅助治疗提供临床依据.方法:多中心随机纳入2015年11月至2016年10月的480例非小细胞肺癌和乳腺癌患者,设立3个实验组(化疗同时分别服用覆参片、覆花片、破壁灵芝孢子粉)和1个空白对照组(单纯化疗).动态监测患者外周血27种细胞因子基线筛选期(第-14至0天)和治疗评估期(第42±7天)的变化,并进行治疗期间体力评分(ECOG)和安全性的评价.结果:480例癌症患者中具有完整临床动态监测数据资料患者共计119例,均衡分布于四组.治疗评估期以单纯化疗组的细胞因子浓度为对比参照,覆参片组白介素(IL)-1ra(P=0.023)、IL-9(P=0.015)、IL-12(P=0.024)、粒细胞集落刺激因子(G-CSF)(P=0.031)、单核细胞趋化因子(MCP-1)(P=0.025)升高;覆花片组IL-4(P=0.005)、IL-5(P=0.009)、IL-7(P=0.026)、IL-10(P=0.026)、IL-12(P=0.038)、IL-15(P=0.014)、G-CSF(P=0.007)升高和干扰素诱导蛋白-10(IP-10)(P=0.012)降低;破壁灵芝孢子粉组IL-2(P<0.001)升高,差异均具有统计学意义.四组患者的ECOG评分与不良事件在组间无统计学差异.结论:三种营养制剂分别与化疗联合使用,可在一定程度上通过调节外周血细胞因子表达来起到调节抗肿瘤免疫反应的效果,且不增加毒副反应.

Dynamic changes of the peripheral T cell receptor (TCR) and soluble receptors and ligands (sRLs) have the potential to be used as biomarkers to monitor the evolution of the immune system in tumor patients undergoing immunotherapy. These functional biomarkers could be used to predict immune response to treatment with immune checkpoint inhibitors (ICIs) and to provide high-value information on the immune function status of cancer patients, thereby helping physicians to make effective clinical decisions. We collected paired pre- and post-treatment peripheral blood samples from 31 solid tumor patients treated with ICIs. TCR and sRL status were investigated using next-generation sequencing and magnetic bead panels. We found that the diversity of the dominant TCR clone at baseline was correlated with durable clinical benefit in patients receiving single-agent treatment. The D50 index, the diversity from the cumulative 50% of the total complementary determinant region 3, was obtained during treatment. A significant difference in progression-free survival was demonstrated between the D50 high and D50 low groups. This result was validated in an independent cohort. A signature including soluble immune checkpoint proteins (sICPs) was identified. Upregulation of the signature during treatment was correlated with durable clinical benefit. All these results indicate that a novel biomarker based on peripheral TCR and sICPs has the potential to be used in prognostic prediction and for rapid determination of therapeutic outcomes in patients treated with immune checkpoint inhibitors.

AbstractBackgroundMolecular testing for alterations in oncogenic driver genes and targeted therapies have become standard procedures for non‐small cell lung cancer (NSCLC) patients. However, little evidence has shed light on the pattern of co‐existence of driver genes in NSCLC, and whether they may have different tumor features affecting immunotherapy is still unclarified.MethodsGenomic alterations in 14 lung cancer‐related genes were conducted in 3440 Chinese NSCLC patients using next‐generation sequencing. Meanwhile, tumor mutational burden and immunotherapy dataset from the Memorial sloan kettering cancer center (MSKCC) and lung adenocarcinoma dataset from The Cancer Genome Atlas (TCGA) were utilized for analyzing the impact of the co‐occurring alterations on patients’ survival following immunotherapy.ResultsIn this cohort, 90.17% of patients had at least one somatic alteration in the 14 genes, including 51% of co‐occurring alterations. TP53 and epidermal growth factor receptor (EGFR) were the most prevalent genes (54.74% and 53.55%, respectively), followed by KRAS, ERBB2, ALK, PIK3CA, ROS1, RET, MET, BRAF, KIT, FGFR1, PDGFRA, and NRAS. The prevalence of TP53, EGFR, and ERBB2 in our cohort were significantly higher than that from the TCGA database, whereas KRAS, BRAF, and PDGFRA were significantly lower than the latter. Furthermore, the patients who harbored multiple alterations (8.86%, 31/350) in eight driver genes survived longer and have a higher tumor mutation burden compared to the patients with a single alteration. Similar result was found between the patients with co‐occurring alteration of EGFR and other driver genes and the patients with single EGFR alteration. Meanwhile, we found a distinct immune cell infiltration feature between patients with single and multiple driver gene alterations, as well as between patients with only EGFR alteration and co‐occurring groups.ConclusionThis study identified a unique driver gene feature and found patients harboring co‐occurring alterations of EGFR and other driver genes may benefit from immunotherapy, which may provide more therapeutic selections for EGFR‐mutated NSCLC patients and merit additional investigation.

目的 探讨真实世界中,程序性死亡受体?1(PD?1)和程序性死亡受体?配体1(PD?L1)抑制剂治疗复发小细胞肺癌(SCLC)的有效性和安全性,并分析潜在的预后相关因素.方法 回顾性分析2015年6月至2019年6月在解放军总医院接受PD?1/PD?L1抑制剂治疗的复发SCLC患者.通过收集患者的基本临床特征、客观缓解率(ORR)、无进展生存期(PFS)、总生存期(OS)及免疫相关不良反应(irAEs)等资料,探讨治疗的临床疗效、不良反应及潜在的预后相关因素.结果 共纳入50例SCLC患者,总体ORR为26.0％,疾病控制率(DCR)为68.0％.至随访截止时间,全组患者的中位PFS为4.1(95％CI:2.6～5.6)个月,中位OS为9.8(95％CI:6.4～13.2)个月.单因素分析结果显示,年龄、病理分期、衍生粒淋比(dNLR)及血清乳酸脱氢酶(LDH)水平与患者PFS相关(P<0.05);年龄、病理分期、KPS评分及LDH水平与患者OS相关(P<0.05).Cox多因素回归分析结果显示,年龄(HR=2.142,95％CI:1.009～4.547,P=0.047)和病理分期(HR=4.533,95％CI:1.958～10.493,P=0.001)是影响SCLC患者PFS的独立预后因素;KPS评分(HR=0.422,95％CI:0.192～0.927,P=0.032)、病理分期(HR=4.542,95％CI:1.553～13.284,P=0.006)及LDH水平(HR=3.799,95％CI:1.703～8.470,P=0.001)是影响SCLC患者OS的独立预后因素.19例患者发生了irAEs,其中疲劳5例(10.0％)、恶心4例(8.0％)、肺炎4例(8.0％)、甲状腺功能紊乱3例(6.0％)、腹泻2例(4.0％)、垂体功能下降1例(2.0％),最严重的irAEs为2例3级肺炎,应用糖皮质激素等处理后好转.结论 在真实世界中,PD?1/PD?L1 抑制剂为复发SCLC 患者带来了生存获益,且不良反应相对可控. 血清 LDH水平可预测复发SCLC患者免疫治疗的OS,有助于选择免疫治疗的潜在获益人群.

Anti-programmed death-1 (PD-1) therapy has been extensively used to treat cancer. Recently, the combination of immunotherapy and anti-angiogenic therapy has emerged as a novel treatment approach. Therefore, we designed a study to evaluate the real-world benefit of the combination of anti-PD-1 and anti-angiogenesis therapy in patients with non-small cell lung cancer (NSCLC).We obtained the medical records of patients at the Chinese People's Liberation Army General Hospital who received either nivolumab or pembrolizumab combined with anti-angiogenesis therapy from January 2015 to December 2018. The overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated for all patients.Sixty-nine patients with NSCLC were included in our study. The ORR was 31.9% (95% CI: 20.6-43.2%) and the median PFS was 8.37 months (95% CI: 6.5-10.0 months). The subgroup analysis statistically revealed a significant difference in ORR for patients receiving first-line treatment vs other lines, and the values were 58.8% (95% CI: 32.7-84.9%) compared with 23.1% (95% CI: 11.2-34.9%). We also observed a significant improvement in PFS, with a median value of 10.5 months (95% CI: 7.4-13.1 months) for patients without EGFR mutations and 5.4 months (95% CI: 4.0-6.3 months) for patients with EGFR mutations.The real-world ORR, PFS, and OS were comparable to previous clinical trials, despite the patients' different baseline characteristics. Importantly, compared with patients having identified EGFR mutations, patients without EGFR mutations had a better PFS. Furthermore, these data support the use of anti-PD-1 combined with anti-angiogenesis therapy as a novel treatment approach for patients with NSCLC.

Abstract Introduction: Immune checkpoint blockade (ICB) targeted to CTLA-4, PD-1, and PD-L1 can promote anti-tumor T cell immunity and clinical responses. Tracking the dynamic changes of the T Cell Repertoire (TCR) can reflect the evolution of the immune system in tumor immunotherapy patients, predict the immune response to ICB, and provide high-value information for clinical monitoring of immune function status of cancer patients to make effective clinical decisions. The purpose of this study was to explore the correlation between the peripheral blood TCR repertoire dynamic changes and the immune response of patients with anti-PD-1/PD-L1, and to accurately guide the individualized treatment of immunotherapy. Methods: To comprehensively profile the TCR repertoire, high-throughput sequencing was used to identify hypervariable rearrangements of complementarity determining region 3 (CDR3) of the TCR β chain in peripheral blood samples from 31 advanced solid tumors (most were non-small cell lung cancer) patients treated with immune checkpoint blockade. The blood samples were obtained at baseline of treatment with PD-1/PD-L1 antibody, one to two additional blood samples were obtained during treatment to assess dynamic changes. Shannon-Wiener index was used to identify the diversity of TCR receptor. D50 index was used to account for diversity from the cumulative 50% of the total CDR3s counted in the sample. Results:Shannon-Wiener index at baseline was higher in durable clinical benefit (CB) group than non-clinical benefit (NCB) group (p value = 0.0040) treated with anti-PD1/PD-L1, and significantly increased in CB group ( p value = 0.031). There is a significant correlation between D50 index and clinical benefit during treatment (p value = 0.025). The higher the D50 index, the more likely it is to have durable clinical benefit. Significant difference in progression-free survival (PFS) rate was identified between the D50 high and D50 low groups (p value = 0.037). We validated this result in an independent cohort of NSCLC patients treated with anti-PD1/PD-L1(N=12). Conclusions:This study revealed the dynamic changes of peripheral blood T cell receptor beta-chain repertoire in patients with solid tumors before and during anti-PD1/PD-L1 treatment. This study found that baseline TCR diversity was associated with clinical efficacy. Patients with durable clinical benefit had an increased overall diversity of TCR. The D50 index of the sample during treatment can reflect whether the patient could benefit from anti-PD1/PD-L1 treatment or not, and was a significant prognostic factor for progression-free (PFS). These analyses provide that the peripheral blood TCR repertoire parameters may be useful for prognosis prediction and rapid determination of therapeutic outcomes for patients treated with immune checkpoint inhibitors. Citation Format: Ye Li, Jiaqian Wang, Shengjie Sun, Liangliang Wu, YunXiao Zhang, Guoqing Zhang, Xiaoting Li, Shunchang Jiao. Dynamics characteristics and prognostic significance of profiling the peripheral blood T-cell receptor repertoire during immune checkpoint blockade in cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3189.

目的 探究肿瘤内科“四生”培训的策略及其效果,为“四生”培训工作的开展提供参考依据.方法 采用考核评分和调查评估的方法,分析本院肿瘤内科个性化“四生”培训工作开展前后的理论和实践考核成绩,调查“四生”对培训模式的认可情况.结果 个性化“四生”培训工作开展后,理论和实践考核成绩均高于培训后,差异有统计学意义(P＜0.05).个性化“四生”培训工作开展后,“四生”各自评情况均优于开展前,差异有统计学意义(P＜0.05).结论 肿瘤内科个性化“四生”培训的开展,对“四生”综合素质的提升和医疗工作的开展均有重要意义.

Aim: A prospective investigation of serum thymidine kinase 1 concentration (STK1p) was performed to evaluate its prognostic value in patients with non-small-cell lung carcinoma (NSCLCs). Patients & methods: The STK1p values of 127 patients were determined by an enhanced chemiluminescent dot blot assay. The patients were recruited from March 2011 to December 2017. Results: Kaplan–Meier plot showed that patients with elevated STK1p values had worse overall survival (OS), especially patients of early/middle stages. Multi-variable COX regression showed that STK1p value and combined treatment surgery + chemotherapy were independent prognostic factors for favorable OS. Conclusion: STK1p is helpful in predicting OS of early/middle stages (I–IIIA) NSCLCs patients following a nonrandomized individual adapted treatment, but is may be not recommended in advanced stages (IIIB + IV) of NSCLCs.

e14152 Background: Immune checkpoint blockade (ICB) targeted to CTLA-4, PD-1, and PD-L1 can promote antitumor T cell immunity and clinical responses. Tracking the dynamic changes of the T Cell Receptor (TCR) Immune Repertoire can reflect the evolution of the immune system in tumor immunotherapy patients, predict the immune response to ICB, and provide high-value information for clinical monitoring of immune function status of cancer patients to make effective clinical decisions. The purpose of this study was to explore the correlation between the peripheral blood TCR repertoire dynamic changes and the immune response of patients with anti-PD-1/PD-L1, and to accurately guide the individualized treatment of immunotherapy. Methods: We sequenced the TCRβ genes from T cells contained in peripheral blood mononuclear cells (PBMCs) from 24 advanced solid tumors patients (PD/7, PR/4, SD/13) treated with immune checkpoint blockade. Peripheral blood samples were collected from baseline, 8-week, and 16-week after treatment for each patient. bioinformatic analysis was used to detect the diversity and clonality changes of TCRβ-CDR3 sequence before and after treatment with ICB in patients, and provide auxiliary technology for further guiding clinical tumor immunotherapy. Results: The analysis result of Chao index showed that the TCR-CDR3 diversity in the PR group was significantly increased after treatment than SD or PD group. (pvalue = 0.001), and the number of CDR3 aa clonotypes also increased significantly (pvalue = 0.012). A total of 61 Vβ gene fragments and 15 Jβ gene fragments were uniquely identified during immunotherapy . There was a significant difference in the number of Vβ gene fragments between baseline samples and after treatment in PR group (pvalue = 0.042). Conclusions: In this project, PBMC samples was used to evaluate the changes of TCR repertoire between before and after treatment with immune checkpoint blockade in advanced solid tumor patients. The immune function status was significantly changed before and after treatment. Patients with PR had significantly increased diversity in TCR repertoire than patients with SD or PD. The results provide T cell receptor β-chain repertoire sequencing and analysis has potential to assess whether immune checkpoint blockade promotes global T cell expansion and/or loss of T cell clonotype diversity, and to identify predictive biomarker for the use of immune checkpoint blockade.