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Introduction: Durvalumab is a check‐point inhibitor against programmed death ligand‐1 (PD‐L1), and anlotinib is a new orally administered multitarget tyrosine kinase inhibitor (TKI). Both agents have been approved in China. Preclinical and clinical trials have suggested that antiangiogenic therapy has the potential to alleviate immunosuppression and showed synergetic effect when combined with ICIs. However, it is unclear that whether this combination is effective when initiated as maintenance treatment in ES‐SCLC patients. Methods: This is a multicenter, randomized, phase II study. A total of 64 eligible patients who do not experience disease progression after four cycles platinum‐based chemotherapy combined with durvalumab will be randomized to durvalumab with anlotinib or durvalumab alone until disease progression, withdrawal of consent, or unacceptable toxicity. The primary endpoint is PFS (from randomization); secondary endpoint was OS and PFS (from diagnosis), objective response rate (ORR); disease control rate (DCR) and duration of response (DOR), safety and tolerability assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Discussion: We conduct a phase II study to investigate the safety and efficacy of durvalumab combined with anlotinib as maintenance treatment in ES‐SCLC patients. [ABSTRACT FROM AUTHOR]

Global phase 3 trials have demonstrated the priority of several next‐generation anaplastic lymphoma kinase‐tyrosine kinase inhibitors (ALK‐TKIs). However, clinical studies are conducted with specific populations that differ from the real world. The study aimed to evaluate the clinical outcomes of alectinib in real‐world settings. Patients with advanced nonsmall‐cell lung cancer (NSCLC) and EML4‐ALK fusion were enrolled from two medical centers between June 2018 and June 2020. The primary endpoints were objective response rate (ORR) and progression‐free survival (PFS) to alectinib. The secondary endpoint was response of brain metastases. The risk factors for disease progression were also investigated. In total, 127 patients with advanced NSCLC were enrolled into this study. Of them, 54.3% received first‐line alectinib. The 1‐ and 2‐year PFS rates were 77.4% and 68.3%, respectively. ORR and disease control rate (DCR) were 53.5% and 91.3%, respectively. Among patients with brain metastases, intracranial ORR and DCR were 63.6% and 88.6%, respectively. In addition, we found that "crizotinib pretreatment", "liver metastasis" and "TP53 co‐mutation" were individually associated with shorter PFS in alectinib treatment. In conclusion, this study confirms the salient clinical outcomes of alectinib for ALK‐fusion‐driven NSCLC patients with or without brain metastases, adding real‐world evidence to the priority of alectinib in clinical practice. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with non-small cell lung cancer but rarely been explored in pulmonary sarcomatoid carcinoma (PSC). This multicenter study aimed to evaluate the effectiveness of ICIs for PSC and its underlying mechanism. Advanced PSC who received ICIs between August 2018 and May 2022 from 11 centers in China were included. Clinical characteristics and treatment information were collected. Whole-exome sequencing (WES) and whole transcriptome sequencing were conducted on pre-treatment samples to explore the mechanism. 113 patients with PSC were enrolled, the median PFS for patients receiving ICIs therapy was 8.77 months (95 % confidence interval, 4.21 to 13.32). Combining ICIs with anti-angiogenic agents significantly increased PFS (p = 0.04). Liver metastasis and combination therapy with anti-angiogenic agents were independent risk factors for PFS (Hazard Ratio [HR] = 3.652, p = 0.019 and HR = 0.435, p = 0.017, respectively). WES showed that PSC presented with a TMB of 6.3 mutations per million base pairs. High expression of TNFα signaling and glycolysis related gene showed a better prognosis. ICIs showed promising benefits for advanced PSC, and the addition of anti-angiogenic therapy might be a more effective treatment strategy for this disease. • The efficacy of ICIs in PSC was poorly explored. • The mPFS for PSC receiving ICIs was 8.77 m (95 % CI, 4.21-13.32). • The addition of anti-angiogenic therapy with ICIs increased PFS of PSC. • The median TMB of PSC was 6.3 mutations per million base pairs. [ABSTRACT FROM AUTHOR]

Background: The study was conducted to compare the effectiveness and safety of pemetrexed/carboplatin or cisplatin/bevacizumab (PemPBev) and paclitaxel/carboplatin/bevacizumab (PacCBev) as first‐line therapy for advanced non‐squamous non‐small cell lung cancer (NS‐NSCLC) patients with wild‐type driver genes in a real‐world setting. Methods: We retrospectively collected the medical records of advanced NS‐NSCLC patients with wild‐type driver genes administered first‐line PemPBev or PacCBev therapy at Shanghai Chest Hospital between January 2014 and June 2016, and analyzed the differences in survival outcomes, efficacy, and safety between PemPBev and PacCBev treatment. Results: A total of 390 patients were included in our analysis: 249 in the PemPBev group and 141 in the PacCBev group. Patients administered PemPBev experienced significantly improved progression‐free survival (PFS) and overall survival (OS) compared to those administered PacCBev (PFS 7.5 vs. 6.2 months, hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.53–0.84, P < 0.001; OS:18.6 vs. 16.0 months, HR 0.68, 95% CI 0.52–0.90, P = 0.002). The objective response rate (ORR) and disease control rate (DCR) were similar between the groups (ORR 21.7% vs. 30.5%, P = 0.053; DCR 69.1% vs. 67.4%, P = 0.728). There was no significant difference in the incidence of adverse events between the groups (64.7% vs. 68.8%; P = 0.407), but the incidence of peripheral neuropathy in the PacCBev group was higher than in the PemPBev group (7.8% vs. 2.4%; P = 0.012). Conclusion: Our study shows that for advanced NS‐NSCLC patients with wild‐type driver genes, first‐line PemPBev might be a better treatment option compared to PacCBev. [ABSTRACT FROM AUTHOR]

Introduction There are a number of uncommon EGFR mutations whose associations with TKIs are not well clarified. Here, we summarize the clinical data of patients with multiple uncommon EGFR mutations and their sensitivity to EGFR TKIs. Methods Between January 2009 and September 2014, we retrospectively examined stage IIIB/IV NSCLC patients harboring uncommon mutations in EGFR at the Shanghai Chest Hospital. Results A total of 123 NSCLC patients harboring uncommon EGFR mutations with treatment and survival details were included in this analysis. 95 Patients who received therapy that consisted of EGFR TKIs experienced a significantly improved overall survival (OS) compared with those who did not receive EGFR TKIs (18.96 months, 95% CI, 16.65–21.26 vs 12.22, 95% CI, 9.17–15.27, p = 0.017). The median progression-free survival (PFS) for patients who harbored the L861Q, G719X, 20ins, Del-19 + L858R, Del-19 or L858R + T790 M, and the Del-19 or L858R + other mutations were 8.90 months (95% CI, 4.47–13.34), 5.98 months (95% CI, 1.53–10.42), 2.00 months (95% CI, 0.00–5.41), 9.53 months (95% CI, 0.00–19.41), 1.94 months (95% CI, 0.00–4.43), and 9.79 months (95% CI, 0.73–18.85), respectively. The best objective response rates (ORRs) for patients who harbored L861Q, G719X, 20ins, Del-19 + L858R, Del-19 or L858R + T790 M, Del-19 or L858R + others were 46.7%, 42.9%, 8.3%, 71.4%, 22.2%, and 55.6%, respectively. Conclusions These results suggest that EGFR TKI therapy is effective in patients with L861Q/G719X/Del-19 + L858R/Del-19 or L858R + other mutations; less effective in patients with 20ins/Del-19 or L858R + T790 M. [ABSTRACT FROM AUTHOR]

• Anlotinib, a novel antiangiogenic multikinase inhibitor, has been approved in China as third-line and above treatment for nonsmall cell lung cancer. • Anlotinib plus TQB2450 demonstrated promising antitumor activities in advanced NSCLC patients without EGFR and ALK alterations and the toxicities were overall manageable. • Anlotinib plus TQB2450 demonstrated promising antitumor activities in pretreated advanced NSCLC without EGFR and ALK alterations. • TQB2450 plus anlotinib for advanced NSCLC patients without driver gene alterations. Immune monotherapy as second-line treatment confers only modest survival benefit on non-small cell lung cancer (NSCLC) patients with no mutated driver genes, necessitating combination treatment strategies. This phase Ib trial investigated the efficacy and safety of anti-PD-L1 antibody TQB2450 plus antiangiogenic drug anlotinib for NSCLC. Pretreated stage IIIB or IV NSCLC patients with wild-type EGFR/ALK and minimally one measurable lesion were randomized 1:1:1 to receive TQB2450 1200 mg plus placebo, or TQB2450 1200 mg plus anlotinib 10 or 12 mg. The primary outcome was progression-free survival (PFS) and the secondary outcomes included objective response rate (ORR). Thirty-three patients received TQB2450 plus placebo and 34 patients each received TQB2450 plus anlotinib 10 mg and 12 mg. At the data cutoff, the median PFS was 8.7 months (95% CI 6.1–17.1) in the TQB2450 plus anlotinib group and 2.8 months (95% CI 1.4–4.7) in the TQB2450 only group. The ORR reached 30.9% (95% CI 20.2%-43.3%) in the TQB2450 plus anlotinib group and was 3.0% (95% CI 0.1%-15.8%) in the TQB2450 only group. In patients with PD-L1 ≥ 1%, the ORR was 50.0% (95% CI 33.4%-66.6%) for TQB2450 plus anlotinib and 5.3% (95% CI 0.1%-26.0%) for TQB2450 plus placebo. No new safety signals were observed. Anlotinib plus TQB2450 demonstrated promising antitumor activities in advanced NSCLC patients without EGFR and ALK alterations and the toxicities were overall manageable. The study findings support the continued development of TQB2450 plus anlotinib for advanced NSCLC patients without driver gene alterations. [ABSTRACT FROM AUTHOR]

Background: Data from studies looking at both EGFR and ERBB2 exon 20 insertion mutations (-20ins) in the same cohort of patients with non-small cell lung cancer (NSCLC) are limited., Objective: The purpose of this study was to analyze EGFR/ERBB2-20ins in all-stage NSCLC patients to reveal their histological and molecular features, and to retrospectively evaluate the results of first-line real-world systemic treatments in patients with advanced-stage disease., Patients and Methods: We collected 13,920 formalin-fixed paraffin-embedded NSCLC specimens. Clinicopathological features were recorded and DNA-based next-generation sequencing was performed. First-line systemic treatment data were obtained via chart review., Results: In total, 414 (2.97%) EGFR-20ins cases and 666 (4.78%) ERBB2-20ins cases were identified. Both were more common in women, non-smokers, and patients with adenocarcinoma. The incidence of EGFR/ERBB2-20ins in adenocarcinoma is inversely proportional to the degree of invasion; 77 and 26 variants were detected in EGFR-20ins and ERBB2-20ins cases, respectively. The most common concurrently mutated genes were TP53 and RB1. In invasive adenocarcinoma, lepidic components were more common in EGFR/ERBB2-20ins-alone cases than in those with other concurrent mutated genes. In EGFR-/ERBB2-20ins patients, there was no significant difference in progression-free survival (PFS) or treatment response to first-line systemic treatments in this study. There was no significant difference in PFS or treatment response among patients with different EGFR/ERBB2-20ins variants and those with or without concurrent mutated genes., Conclusions: EGFR/ERBB2-20ins is more common in early lung adenocarcinoma. EGFR-20ins had more variants. In both cohorts, the results for first-line systemic treatments showed no significant difference., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Despite the remarkable clinical advance of immune checkpoint inhibitors (ICIs) in the treatment of lung cancer, there are limited studies focused on evaluating efficacy of ICIs for patients with human epidermal growth factor receptor 2 (HER2)-mutant lung adenocarcinoma., Methods: We conducted a multicenter retrospective study of patients with HER2-mutant lung adenocarcinoma who received ICIs therapy at Shanghai Pulmonary Hospital, Shanghai Chest Hospital and the First Affiliated Hospital of Wenzhou Medical University between 2016 and 2021. Response was defined with reference to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1., Results: Among the 26 patients enrolled in our study, the overall objective response rate (ORR) was 38.5%, disease control rate (DCR) was 84.6% and median progression-free survival (PFS) was 7.4 months. Majority of patients were treated with immunochemotherapy combination regimens (16/26, 61.5%), with a median PFS of 8.4 months. Among the 9 patients receiving ICIs-based therapy as first-line treatment, 5 patients had partial response (PR) and 4 patients had stable disease (SD), with a median PFS of 9.1 months. Of the entire cohort, 5 patients who received ICIs before epidermal growth factor receptor (EGFR)/HER2-targeting drugs achieved a median PFS of 8.4 months., Conclusion: Our retrospective study provides clinical evidence that front line of ICIs-based therapy is also worth considering for the treatment to improve survival outcomes of patients with HER2-mutant lung adenocarcinoma., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Small cell lung cancer (SCLC) is the most malignant lung cancer. Some of them are mixed with non-small cell lung cancer(NSCLC, Non SCLC),which are called combined small cell lung cancer (C-SCLC).Due to the difficulty of pathological diagnosis and the complexity of treatment, studies of C-SCLC have just been rising in recent years. This study is to evaluate the clinical and pathologic characteristics of C-SCLC., Methods: Stage Ⅰ-Ⅲa C-SCLC patients who received radical R0 surgery between 2009-2018 in Shanghai Chest Hospital were enrolled. Clinical characteristics and prognosis were analyzed., Results: Totally 181 patients were included, most of them were small cell combined with large cell neuroendocrine components(SCLC/LCNEC,58.0 %,N = 105),then with adenocarcinoma(SCLC/ADC:13.8 %,N = 25),and finally with squamous cell carcinoma(SCLC/SCC:13.3 %,N = 24).Median DFS and OS of C-SCLC patients underwent radical surgery were 32.5 and 49.7 months.1,3 and 5 years DFS rates of the entire cohort were 68.5 %,32.6 % and 16.0 %,respectively. Patients with SCLC/LCNEC had longer DFS (44.1 m vs. 20.4 m, p = 0.040) and longer OS trend (62.1 m vs. 33.2 m, p = 0.122).Groups of whether tumor invaded the pleura(p = 0.028 and p = 0.050),lymph node stage(p = 0.029 and p = 0.010) and the courses of adjuvant chemotherapy(p = 0.011 and p = 0.001) had statistical differences on DFS and OS., Conclusions: SCLC/LCNEC was the most common type of C-SCLC. Patients' DFS and OS were also longer than other combined types. Adjuvant chemotherapy for SCLC is still the main treatment for surgical C-SCLC. Further studies are needed to clarify the clinical characteristics and prognosis of C-SCLC., Competing Interests: Declaration of Competing Interest We declare no any interest conflict., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: It has previously been demonstrated that surgically resected small-cell lung cancer (SCLC) patients could benefit from prophylactic cranial irradiation (PCI). However, PCI in patients without lymph node involvement remains controversial. This study includes a larger sample size to evaluate the benefit of PCI therapy in this specific population., Methods: The records of surgically resected SCLC patients without lymph node involvement (N0M0) in Shanghai Chest Hospital were retrospectively reviewed., Results: Between January 2006 and May 2017, a total of 146 cases of surgically resected SCLC without lymph node involvement were included. A total of 46 patients received PCI therapy and 100 patients received no therapy. During the observation period, 12.0% (12/100) of the patients who did not receive PCI therapy developed brain metastases while 10.9% (5/46) of patients who received PCI therapy developed brain metastases. With regard to time to recurrence, no significant difference was observed among the groups (P = 0.798). Moreover, there was no significant difference in either the overall survival benefit (hazard ratio [HR] = 0.84, 95% confidence interval [CI]: 0.49-1.45, P = 0.532) or disease-free survival rate (HR = 0.95, 95% CI: 0.52-1.75, P = 0.864)., Conclusions: The evidence obtained does not support PCI therapy in the management of surgically resected SCLC with no lymph node involvement., Key Points: Prophylactic cranial irradiation (PCI) remains controversial for resected small-cell lung cancer (SCLC) without lymph node involvement. In this study, the results indicated that PCI does not reduce the risk of cerebral recurrence of resected p-T1-2N0M0 SCLC. This is the largest sample size study focused on PCI in resected p-T1-2N0M0 SCLC. Future revised versions of the guidelines should address this issue., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: This study aimed to explore adjuvant chemotherapy (ACT) candidates based on a recurrence risk-scoring model in completely lobectomized stage I patients with lung adenocarcinoma (LAD)., Methods: A retrospective study was performed on 4606 patients (non-ACT group: n = 3514; ACT group: n = 1092) who underwent complete lobectomy for LAD at Shanghai Chest Hospital from 2008 to 2014. The nomogram predicting recurrence-free survival (RFS) was developed in the non-ACT group using Cox proportional hazards regression. The nomogram-based risk score was calculated in the entire cohort. Differences of RFS between the non-ACT and ACT groups were compared as stratified by the risk score. The score cut-off points were determined using the X-tile software., Results: Six independent predictors, including age, sex, tumor size, pathological subtype, visceral pleural invasion (VPI), and lymphovascular invasion (LVI) were associated with RFS. The nomogram more accurately predicted RFS than the 8th TNM staging {C-index: 0.784 [95% confidence interval (CI) 0.756-0.812] vs. 0.719 (95% CI 0.689-0.749), p = 0.0017}. A significant RFS difference was observed among the low-, intermediate- and high-risk groups (p < 0.0001), as divided by the optimal cut-points of risk score (203 and 244). ACT did not improve RFS for patients at intermediate-risk, or was even detrimental for low-risk patients; however, improved RFS was observed in ACT receivers at high-risk (p = 0.0416). ACT candidates with a risk score ≥ 245 constituted 2.6% of stage I patients., Conclusions: The nomogram provided an individual prediction of RFS for stage I LAD following lobectomy. High-risk patients (score ≥ 245) may benefit from postoperative ACT.