Liyun Miao

Early monitoring biomarkers for first-line chemoimmunotherapy in extensive-stage small-cell lung cancer (SCLC) remain limited. Dynamic blood-based changes may better reflect treatment-related alterations than static baseline values. We conducted a retrospective multicenter study comprising a 225-patient baseline cohort, a 148-patient dynamic development cohort of chemoimmunotherapy-treated patients with paired baseline/post-cycle 2 blood tests, and a 49-patient independent external validation cohort. Early relative changes in routine blood-based markers were analyzed for associations with objective response rate (ORR) and survival. A simplified ImmunoScore based on standardized changes in neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) was developed and externally validated. Elevated baseline NLR, platelet-to-lymphocyte ratio (PLR), LDH, and D-dimer were associated with shorter overall survival (OS), whereas only LDH remained independently prognostic. In the development cohort, ΔNLR showed the strongest association with ORR, and both ΔNLR and ΔLDH were associated with progression-free survival (PFS). The ImmunoScore achieved areas under the curve (AUCs) of 0.895 and 0.938 for ORR prediction in the development and external validation cohorts. The ImmunoScore may provide an interpretable post-cycle 2 framework for ORR prediction and subsequent survival stratification in SCLC. Given the small external validation cohort, these findings remain exploratory and require prospective multicenter validation.

Lung cancer remains one of the most prevalent and lethal malignancies globally and its treatment has consistently been a focal point of research in the medical field. The emergence of immunotherapies such as immune checkpoint inhibitors has brought about a new understanding of vaccine treatment for tumors. Tumor vaccines induce anti-tumor immune responses by targeting tumor-associated antigens or specific neoantigens. In recent years, advancements in vaccine technology, such as neoantigen screening, refinement of vector systems, and optimization of adjuvants, have significantly propelled the development of personalized tumor vaccines, thereby endowing lung cancer vaccines with substantial therapeutic potential. Furthermore, studies have demonstrated that the integration of tumor vaccines with immune checkpoint inhibitors, chemotherapy, and other therapeutic modalities can produce synergistic anti-tumor effects. This article reviews the latest progress in lung cancer vaccines, elucidates current combination treatment strategies supported by preclinical and clinical evidence, and explores their translational potential for clinical application.

Lung cancer is the leading cause of cancer-related death globally. Despite various treatment options, adverse reactions and treatment resistance limit their clinical application and efficacy, therefore, new effective treatment options are still needed. Oncolytic viruses (OVs) are a new anti-cancer option. With a powerful anti-tumor effect, OVs are gradually being applied to the treatment of solid tumor. In clinical practice, we have found that in patients with NSCLC and SCLC, OVs combined with immune checkpoint inhibitors (ICI) treatment make tumor with poor response to immunotherapy become sensitive. Furthermore, studies have shown that OVs combined with chemotherapy, radiation therapy, and other immune approaches (such as anti-pd1 drugs) have synergistic effects. These studies suggest that OVs combined therapy may bring hope for the treatment of lung cancer patients. This article will review the current status and prospect of OVs combination therapy in the field of lung cancer treatment and summarizes the mechanism of action.

Antibody–drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)‐positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2‐expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2‐positive and HER2‐low breast cancer, HER2‐positive gastric cancer, and HER2‐mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti‐HER2 ADC therapy. Studies on anti‐HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti‐HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti‐HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti‐HER2 ADC therapy in clinical practice.

Background: Maintenance therapy could significantly improve the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. Anlotinib is effective, tolerable, and convenient in administration as a third-line treatment for NSCLC. This study aimed to evaluate the efficacy and safety of maintenance therapy with anlotinib after platinum-based induction chemotherapy for patients with advanced NSCLC. Methods: This pooled analysis of 2 multicenter, open-label, single-arm, phase 2 clinical trials (ALTER-L014 and ALTER-L011) enrolled patients with locally advanced or metastatic NSCLC and without known sensitive mutations in China between September 2018 and January 2021. The primary outcome was progression-free survival. The secondary outcomes were objective response rate, disease control rate, overall survival, and safety. Results: The data of 23 patients were pooled, with 15 from ALTER-L014 and 8 from ALTER-L011. At the cutoff date of June 13, 2021, the median progression-free survival since the start of maintenance therapy was 5.95 (95% confidence interval, 4.30–8.80) months. Nineteen patients had stable disease, 1 had a partial response and 3 had progressive disease. The objective response rate was 4.35%, while disease control rate was 86.96%. The median overall survival of the patients since the start of maintenance therapy was 18.60 (95% confidence interval, 6.87–22.80) months. The incidence of adverse events of grade ≥ 3 was 21.7%. Conclusion: Anlotinib might offer a new option for maintenance treatment in patients with locally advanced or metastatic NSCLC without known sensitive mutations after standard first-line platinum-based chemotherapy.

The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Purpose: Anlotinib is widely used in the clinical treatment of non-small cell lung cancer (NSCLC), alone or in combination with other anticancer drugs. The aim of this study was to investigate the real-world efficacy and safety of anlotinib-containing regimens. Patients and Methods: Confirmed advanced NSCLC patients who had received anlotinib alone or in combination were enrolled. An overall analysis of the efficacy and safety of anlotinib was performed in all patients, and then subgroup analysis was used to further compare the efficacy between anlotinib monotherapy and combination therapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were ADR, ORR, and DCR. Results: A total of 240 patients were included. The overall median PFS was 8.5 months (95% confidence interval [CI]: 7.1– 9.9 months). Anlotinib treatment regimens (monotherapy or combination therapy) and whether they received previous antiangiogenesis were associated with PFS. Anlotinib plus immunotherapy achieved longer PFS than anlotinib monotherapy (median PFS: 10.5 vs 6.5 months, p=0.007). Stratification analysis showed the PFS of anlotinib plus immunotherapy was significantly longer in male, adenocarcinoma, <=65 years old, patients stage IV, EGFR wild type, with extrathoracic metastasis, performance status scores ≥ 2, the first-line treatment, patients with a history of hypertension and no previous antiangiogenesis than anlotinib monotherapy. The median PFS of anlotinib plus chemotherapy, targeted therapy was slightly longer than anlotinib alone (respectively, 10.5 vs 6.5 months, p=0.095; 9.5 vs 6.5 months, p=0.177). Adverse reactions were mostly mild and acceptable, with hypertension being the most common. Conclusion: Anlotinib is effective and tolerable in advanced NSCLC patients. Immunotherapy combination with anlotinib significantly improved PFS. The efficacy of anlotinib may be impaired by previous antiangiogenic therapy, which can be investigated in further studies.

Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up.

Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first‐ and second‐line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow‐up of TETs.

PURPOSE: The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients (N = 465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety. RESULTS: At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS, 8.4 v 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P < .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P = .0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P = .026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values ≤ .001). CONCLUSION: Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.